Neurodegeneration is an early event in diabetic retinopathy:therapeutic implications

Diabetic retinopathy (DR) remains the leading cause of blindness among working-age individuals in developed countries. Current treatments for DR are indicated in advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of DR are needed. DR has been classically considered to be a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the underlying mechanisms that lead to neurodegeneration will be essential for identifying new therapeutic targets. From the clinical point of view, the identification of those patients in whom retinal neurodegeneration appears will be crucial for implementing early treatment based on neuroprotective drugs. When the early stages of DR are the therapeutic target, it would be inconceivable to recommend an aggressive treatment such as intravitreous injections. By contrast, topical administration of neuroprotective drugs by using eye drops is a possible option. However, clinical trials to determine the safety and effectiveness of this non-invasive route, as well as a standardisation of the methods for monitoring neurodegeneration, are needed.

Tablet App halometer for the assessment of dysphotopsia

Purpose To assess the validity and repeatability of the Aston Halometer. Setting University clinic, United Kingdom. Design Prospective, repeated-measures experimental study. Methods The halometer comprises a bright light-emitting-diode (LED) glare source in the center of an iPad4. Letters subtending 0.21° (∼0.3 logMAR) were moved centrifugally from the LED in 0.05 degree steps in 8 orientations separated by 45 degrees for each of 4 contrast levels (1000, 500, 100, and 25 Weber contrast units [Cw]) in random order. Bangerter occlusion foils were inserted in front of the right eye to simulate monocular glare conditions in 20 subjects (mean age 27.7 ± 3.1 years). Subjects were positioned 2 meters from the screen in a dark room with the iPad controlled from an iPhone via Bluetooth operated by the researcher. The C-Quant straylight meter was also used with each of the foils to measure the level of straylight over the retina. Halometry and straylight repeatability was assessed at a second visit. Results Halo size increased with the different occlusion foils and target contrasts (F = 29.564, P <.001) as expected and in a pattern similar to straylight measures (F = 80.655, P <0.001). Lower contrast letters showed better sensitivity but larger glare-obscured areas, resulting in ceiling effects caused by the screen's field-of-view, with 500 Cw being the best compromise. Intraobserver and interobserver repeatability of the Aston Halometer was good (500Cw: 0.84 to 0.93 and 0.53 to 0.73) and similar to the straylight meter. Conclusion The halometer provides a sensitive, repeatable way of quantifying a patient-recognized form of disability glare in multiple orientations to add objectivity to subjectively reported discomfort glare.

Cross-orientation masking is speed invariant between ocular pathways but speed dependent within them

In human (D. H. Baker, T. S. Meese, & R. J. Summers, 2007b) and in cat (B. Li, M. R. Peterson, J. K. Thompson, T. Duong, & R. D. Freeman, 2005; F. Sengpiel & V. Vorobyov, 2005) there are at least two routes to cross-orientation suppression (XOS): a broadband, non-adaptable, monocular (within-eye) pathway and a more narrowband, adaptable interocular (between the eyes) pathway. We further characterized these two routes psychophysically by measuring the weight of suppression across spatio-temporal frequency for cross-oriented pairs of superimposed flickering Gabor patches. Masking functions were normalized to unmasked detection thresholds and fitted by a two-stage model of contrast gain control (T. S. Meese, M. A. Georgeson, & D. H. Baker, 2006) that was developed to accommodate XOS. The weight of monocular suppression was a power function of the scalar quantity ‘speed’ (temporal-frequency/spatial-frequency). This weight can be expressed as the ratio of non-oriented magno- and parvo-like mechanisms, permitting a fast-acting, early locus, as befits the urgency for action associated with high retinal speeds. In contrast, dichoptic-masking functions superimposed. Overall, this (i) provides further evidence for dissociation between the two forms of XOS in humans, and (ii) indicates that the monocular and interocular varieties of XOS are space/time scale-dependent and scale-invariant, respectively. This suggests an image-processing role for interocular XOS that is tailored to natural image statistics—very different from that of the scale-dependent (speed-dependent) monocular variety.

Video normals from colored lights

We present an algorithm and the associated single-view capture methodology to acquire the detailed 3D shape, bends, and wrinkles of deforming surfaces. Moving 3D data has been difficult to obtain by methods that rely on known surface features, structured light, or silhouettes. Multispectral photometric stereo is an attractive alternative because it can recover a dense normal field from an untextured surface. We show how to capture such data, which in turn allows us to demonstrate the strengths and limitations of our simple frame-to-frame registration over time. Experiments were performed on monocular video sequences of untextured cloth and faces with and without white makeup. Subjects were filmed under spatially separated red, green, and blue lights. Our first finding is that the color photometric stereo setup is able to produce smoothly varying per-frame reconstructions with high detail. Second, when these 3D reconstructions are augmented with 2D tracking results, one can register both the surfaces and relax the homogenous-color restriction of the single-hue subject. Quantitative and qualitative experiments explore both the practicality and limitations of this simple multispectral capture system.

Self-calibrated, multi-spectral photometric stereo for 3D face capture

This paper addresses the problem of obtaining 3d detailed reconstructions of human faces in real-time and with inexpensive hardware. We present an algorithm based on a monocular multi-spectral photometric-stereo setup. This system is known to capture high-detailed deforming 3d surfaces at high frame rates and without having to use any expensive hardware or synchronized light stage. However, the main challenge of such a setup is the calibration stage, which depends on the lights setup and how they interact with the specific material being captured, in this case, human faces. For this purpose we develop a self-calibration technique where the person being captured is asked to perform a rigid motion in front of the camera, maintaining a neutral expression. Rigidity constrains are then used to compute the head's motion with a structure-from-motion algorithm. Once the motion is obtained, a multi-view stereo algorithm reconstructs a coarse 3d model of the face. This coarse model is then used to estimate the lighting parameters with a stratified approach: In the first step we use a RANSAC search to identify purely diffuse points on the face and to simultaneously estimate this diffuse reflectance model. In the second step we apply non-linear optimization to fit a non-Lambertian reflectance model to the outliers of the previous step. The calibration procedure is validated with synthetic and real data.

Blobs versus bars:psychophysical evidence supports two types of orientation response in human color vision

The classic hypothesis of Livingstone and Hubel (1984, 1987) proposed two types of color pathways in primate visual cortex based on recordings from single cells: a segregated, modularpathway that signals color but provides little information about shape or form and a second pathway that signals color differences and so defines forms without the need to specify their colors. A major problem has been to reconcile this neurophysiological hypothesis with the behavioral data. A wealth of psychophysical studies has demonstrated that color vision has orientation-tuned responses and little impairment on form related tasks, but these have not revealed any direct evidence for nonoriented mechanisms. Here we use a psychophysical method of subthreshold summation across orthogonal orientations for isoluminant red-green gratings in monocular and dichoptic viewing conditions to differentiate between nonoriented and orientation-tuned responses to color contrast. We reveal nonoriented color responses at low spatial frequencies (0.25-0.375 c/deg) under monocular conditions changing to orientation-tuned responses at higher spatial frequencies (1.5 c/deg) and under binocular conditions. We suggest that two distinct pathways coexist in color vision at the behavioral level, revealed at different spatial scales: one is isotropic, monocular, and best equipped for the representation of surface color, and the other is orientation-tuned, binocular, and selective for shape and form. This advances our understanding of the organization of the neural pathways involved in human color vision and provides a strong link between neurophysiological and behavioral data. © 2013 ARVO.

Visual outcomes and subjective experience after bilateral implantation of a new diffractive trifocal intraocular lens

Purpose - To assess clinical outcomes and subjective experience after bilateral implantation of a diffractive trifocal intraocular lens (IOL). Setting - Midland Eye Institute, Solihull, United Kingdom. Design - Cohort study. Methods - Patients had bilateral implantation of Finevision trifocal IOLs. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and manifest refraction were measured 2 months postoperatively. Defocus curves were assessed under photopic and mesopic conditions over a range of +1.50 to -4.00 diopters (D) in 0.50 D steps. Contrast sensitivity function was assessed under photopic conditions. Halometry was used to measure the angular size of monocular and binocular photopic scotomas arising from a glare source. Patient satisfaction with uncorrected near vision was assessed using the Near Activity Visual Questionnaire (NAVQ). Results - The mean monocular CDVA was 0.08 logMAR ± 0.08 (SD) and the mean binocular CDVA, 0.06 ± 0.08 logMAR. Defocus curve testing showed an extended range of clear vision from +1.00 to -2.50 D defocus, with a significant difference in acuity between photopic conditions and mesopic conditions at -1.50 D defocus only. Photopic contrast sensitivity was significantly better binocularly than monocularly at all spatial frequencies. Halometry showed a glare scotoma of a mean size similar to that in previous studies of multifocal and accommodating IOLs; there were no subjective complaints of dysphotopsia. The mean NAVQ Rasch score for satisfaction with near vision was 15.9 ± 10.7 logits. Conclusions - The trifocal IOL implanted binocularly produced good distance visual acuity and near and intermediate visual function. Patients were very satisfied with their uncorrected near vision.

The vision strategy of golf putting

Golfers, coaches and researchers alike, have all keyed in on golf putting as an important aspect of overall golf performance. Of the three principle putting tasks (green reading, alignment and the putting action phase), the putting action phase has attracted the most attention from coaches, players and researchers alike. This phase includes the alignment of the club with the ball, the swing, and ball contact. A significant amount of research in this area has focused on measuring golfer’s vision strategies with eye tracking equipment. Unfortunately this research suffers from a number of shortcomings, which limit its usefulness. The purpose of this thesis was to address some of these shortcomings. The primary objective of this thesis was to re-evaluate golfer’s putting vision strategies using binocular eye tracking equipment and to define a new, optimal putting vision strategy which was associated with both higher skill and success. In order to facilitate this research, bespoke computer software was developed and validated, and new gaze behaviour criteria were defined. Additionally, the effects of training (habitual) and competition conditions on the putting vision strategy were examined, as was the effect of ocular dominance. Finally, methods for improving golfer’s binocular vision strategies are discussed, and a clinical plan for the optometric management of the golfer’s vision is presented. The clinical management plan includes the correction of fundamental aspects of golfers’ vision, including monocular refractive errors and binocular vision defects, as well as enhancement of their putting vision strategy, with the overall aim of improving performance on the golf course. This research has been undertaken in order to gain a better understanding of the human visual system and how it relates to the sport performance of golfers specifically. Ultimately, the analysis techniques and methods developed are applicable to the assessment of visual performance in all sports.

Value of glycaemic control in diabetes

Full text: Several Lancet publications have questioned the value of glycaemic control in diabetic patients. For example, in their Comment (Sept 29, p 1103),1 John Cleland and Stephen Atkin state that “Improved glycaemic control is not a surrogate for effective care of patients who have diabetes”, and Victor Montori and colleagues (p 1104)2 claim that “HbA1c loses its validity as a surrogate marker when patients have a constellation of metabolic abnormalities”. We are concerned that the reaction against “glucocentricity” in the field of diabetes has gone too far. Even the UK's National Prescribing Centre website, carrying the National Health Service logo, includes comments that undermine the value of glycaemic control. For example, referring to the United Kingdom Prospective Diabetes Study (UKPDS), this site states that “Compared with ‘conventional control’ there was no benefit from tight control of blood glucose with sulphonylureas or insulin with regard to total mortality, diabetes-related death, macrovascular outcomes or microvascular outcomes, including all the most serious ones such as blindness or kidney failure”.3 It is well established that better glycaemic control reduces long-term microvascular complications in type 1 and type 2 diabetes.4 In type 2 diabetes, the UKPDS reported that a composite microvascular endpoint (retinopathy requiring photocoagulation, vitreous haemorrhage, and fatal or non-fatal renal failure) was reduced by 25% in patients randomised to intensive glucose control (p=0·0099).4 To imply that these are not patient-relevant outcomes is to distort the evidence. Many studies have also found that improved glycaemic control reduces macrovascular complications.5 Do not be misled: glycaemic control remains a crucial component in the care of people with diabetes. The authors have received research support and undertaken ad hoc consultancies and speaker engagements for several pharmaceutical companies.

Genetic risk factors and age-related macular degeneration (AMD)

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make lifestyle choices that may reduce the risk of disease. Collaboration between geneticists, ophthalmologists, and optometrists suggests that genetic risk factors play a more significant role in AMD than previously thought. The most important genes are associated with immune system modulation and the complement system, e.g., complement factor H (CFH), factor B (CFB), factor C3, and serpin peptidase inhibitor (SERPING1). Genes associated with membrane transport, e.g., ATP-binding cassette protein (ABCR) and voltage-dependent calcium channel gamma 3 (CACNG3), the vascular system, e.g., fibroblast growth factor 2 (FGF2), fibulin-5, lysyl oxidase-like gene (LOXL1) and selectin-P (SELP), and with lipid metabolism, e.g., apolipoprotein E (APOE) and hepatic lipase (LIPC) have also been implicated. In addition, several other genes exhibit some statistical association with AMD, e.g., age-related maculopathy susceptibility protein 2 (ARMS2) and DNA excision repair protein gene (ERCC6) but more research is needed to establish their significance. Modifiable risk factors for AMD should be discussed with patients whose lifestyle and/or family history place them in an increased risk category. Furthermore, calculation of AMD risk using current models should be recommended as a tool for patient education. It is likely that AMD management in future will be increasingly influenced by assessment of genetic risk as such screening methods become more widely available. © 2013 Spanish General Council of Optometry.

Reading without central vision:effects of text spacing on reading in patients with macular disease

Abstract: Loss of central vision caused by age-related macular degeneration (AMD) is a problem affecting increasingly large numbers of people within the ageing population. AMD is the leading cause of blindness in the developed world, with estimates of over 600,000 people affected in the UK . Central vision loss can be devastating for the sufferer, with vision loss impacting on the ability to carry out daily activities. In particular, inability to read is linked to higher rates of depression in AMD sufferers compared to age-matched controls. Methods to improve reading ability in the presence of central vision loss will help maintain independence and quality of life for those affected. Various attempts to improve reading with central vision loss have been made. Most textual manipulations, including font size, have led to only modest gains in reading speed. Previous experimental work and theoretical arguments on spatial integrative properties of the peripheral retina suggest that ‘visual crowding’ may be a major factor contributing to inefficient reading. Crowding refers to the phenomena in which juxtaposed targets viewed eccentrically may be difficult to identify. Manipulating text spacing of reading material may be a simple method that reduces crowding and benefits reading ability in macular disease patients. In this thesis the effect of textual manipulation on reading speed was investigated, firstly for normally sighted observers using eccentric viewing, and secondly for observers with central vision loss. Test stimuli mimicked normal reading conditions by using whole sentences that required normal saccadic eye movements and observer comprehension. Preliminary measures on normally-sighted observers (n = 2) used forced-choice procedures in conjunction with the method of constant stimuli. Psychometric functions relating the proportion of correct responses to exposure time were determined for text size, font type (Lucida Sans and Times New Roman) and text spacing, with threshold exposure time (75% correct responses) used as a measure of reading performance. The results of these initial measures were used to derive an appropriate search space, in terms of text spacing, for assessing reading performance in AMD patients. The main clinical measures were completed on a group of macular disease sufferers (n=24). Firstly, high and low contrast reading acuity and critical print size were measured using modified MNREAD test charts, and secondly, the effect of word and line spacing was investigated using a new test, designed specifically for this study, called the Equal Readability Passages (ERP) test. The results from normally-sighted observers were in close agreement with those from the group of macular disease sufferers. Results show that: (i) optimum reading performance was achieved when using both double line and double word spacing; (ii) the effect of line spacing was greater than the effect of word spacing (iii) a text size of approximately 0.85o is sufficiently large for reading at 5o eccentricity. In conclusion, the results suggest that crowding is detrimental to reading with peripheral vision, and its effects can be minimized with a modest increase in text spacing.

Designing a mobile diet diary application with and for older adults with AMD:a case ctudy

Age-Related Macular Degeneration (AMD) is the UK’s leading cause of severe visual impairment amongst the elderly. It accounts for 16,000 blind/partial sight registrations per year and is the leading cause of blindness among people aged 55 years and older in western countries (Bressler, 2004). Our research aims to design and develop a self-monitoring, ability-reactive technology (SMART) for users with AMD to support their dietary-based AMD risk mitigation and progression retardation over time. In this paper, we reflect on our experience of adapting and applying a participatory design (PD) approach to support the effective design of our application with and for older adults with AMD. We introduce the outcome of a series of PD sessions with older adults with AMD - that is, a paper prototype of our proposed application which focuses on accessibility for our target users - and discuss implications for the eventual prototype development

A safety evaluation of ranibizumab in the treatment of age-related macular degeneration

Introduction: The use of intravitreal ranibizumab has transformed the outcomes for thousands of patients with wet age related macular degeneration (AMD), which is the leading cause of blindness in developed countries. Prior to its introduction, most patients with wet AMD would rapidly lose central vision. The use of intravitreal ranibizumab has been shown to reduce certifiable visual loss by about a half. Current treatment regimens with ranibizumab in wet AMD require multiple injections over several years and so it is highly relevant to review the safety record of this important drug.Areas covered: This review considers the important ocular and systemic adverse events (AE) that have been reported in the literature, particularly in the context of the pivotal clinical trials that have been performed. It also reviews the safety of other anti-VEGF drugs that are used in wet AMD, namely bevacizumab and aflibercept, and compares these drugs with ranibizumab.Expert opinion: Overall, intravitreal ranibizumab can be considered a safe and highly effective drug for patients with wet AMD. However recent concerns about retinal thinning following ranibizumab therapy, possible systemic AE associated with all anti-VEGF drugs and the occurrence of complications relating to drug preparation and delivery must be considered. © 2014 Informa UK, Ltd.

Visual performance of a new bi-aspheric, segmented, asymmetric multifocal IOL

PURPOSE: To assess the visual performance and subjective experience of eyes implanted with a new bi-aspheric, segmented, multifocal intraocular lens: the Mplus X (Topcon Europe Medical, Capelle aan den IJssel, Netherlands). METHODS: Seventeen patients (mean age: 64.0 ± 12.8 years) had binocular implantation (34 eyes) with the Mplus X. Three months after the implantation, assessment was made of: manifest refraction; uncorrected and corrected distance visual acuity; uncorrected and distance corrected near visual acuity; defocus curves in photopic conditions; contrast sensitivity; halometry as an objective measure of glare; and patient satisfaction with unaided near vision using the Near Acuity Visual Questionnaire. RESULTS: Mean residual manifest refraction was -0.13 ± 0.51 diopters (D). Twenty-five eyes (74%) were within a mean spherical equivalent of ±0.50 D. Mean uncorrected distance visual acuity was +0.10 ± 0.12 logMAR monocularly and 0.02 ± 0.09 logMAR binocularly. Thirty-two eyes (94%) could read 0.3 or better without any reading correction and all patients could read 0.3 or better with a reading correction. Mean monocular uncorrected near visual acuity was 0.18 ± 0.16 logMAR, improving to 0.15 ± 0.15 logMAR with distance correction. Mean binocular uncorrected near visual acuity was 0.11 ± 0.11 logMAR, improving to 0.09 ± 0.12 logMAR with distance correction. Mean binocular contrast sensitivity was 1.75 ± 0.14 log units at 3 cycles per degree, 1.88 ± 0.20 log units at 6 cycles per degree, 1.66 ± 0.19 log units at 12 cycles per degree, and 1.11 ± 0.20 log units at 18 cycles per degree. Mean binocular and monocular halometry showed a glare profile of less than 1° of debilitating light scatter. Mean Near Acuity Visual Questionnaire Rasch score (0 = no difficulty, 100 = extreme difficulty) for satisfaction for near vision was 20.43 ± 14.64 log-odd units. CONCLUSIONS: The Mplus X provides a good visual outcome at distance and near with minimal dysphotopsia. Patients were very satisfied with their uncorrected near vision. © SLACK Incorporated.

Refractive error, cognitive demand and nearwork-induced transient myopia

Purpose. Whereas many previous studies have identified the association between sustained near work and myopia, few have assessed the influence of concomitant levels of cognitive effort. This study investigates the effect of cognitive effort on near-work induced transient myopia (NITM). Methods. Subjects comprised of six early onset myopes (EOM; mean age 23.7 yrs; mean onset 10.8 yrs), six late-onset myopes (LOM; mean age 23.2 yrs; mean onset 20.0 yrs) and six emmetropes (EMM; mean age 23.8 yrs). Dynamic, monocular, ocular accommodation was measured with the Shin-Nippon SRW-5000 autorefractor. Subjects engaged passively or actively in a 5 minute arithmetic sum checking task presented monocularly on an LCD monitor via a Badal optical system. In all conditions the task was initially located at near (4.50 D) and immediately following the task instantaneously changed to far (0.00 D) for a further 5 minutes. The combinations of active (A) and passive (P) cognition were randomly allocated as P:P; A:P; A:A; P:A. Results. For the initial near task, LOMs were shown to have a significantly less accurate accommodative response than either EOMs or EMMs (p < 0.001). For the far task, post hoc analyses for refraction identified EOMs as demonstrating significant NITM compared to LOMs (p < 0.05), who in turn showed greater NITM than EMMs (p < 0.001). The data show that for EOMs the level of cognitive activity operating during the near and far tasks determines the persistence of NITM; persistence being maximal when active cognition at near is followed by passive cognition at far. Conclusions. Compared with EMMs, EOMs and LOMs are particularly susceptible to NITM such that sustained near vision reduces subsequent accommodative accuracy for far vision. It is speculated that the marked NITM found in EOM may be a consequence of the crystalline lens thinning shown to be a developmental feature of EOM. Whereas the role of small amounts of retinal defocus in myopigenesis remains equivocal, the results show that account needs to be taken of cognitive demand in assessing phenomena such as NITM.