Quality-of-life and clinical outcomes in age-related macular degeneration

Age-related macular degeneration (AMD) is of increasing concern given the ageing population, and the associated economic and social burdens. Vision-related quality-of-life (QoL) is arguably one of the most important factors in the management of those with AMD. Consequently, there is a clear need for an understanding of the clinical outcomes that influence vision-related QoL in order to inform management strategies. The principle aim of the studies described herein was to determine the factors that predict vision-related QoL in those with AMD, over 1 year. Experimental procedures were undertaken at baseline (n=52 individuals with AMD) and repeated after 1 year (n=32 individuals with AMD). These included: visual acuity, contrast sensitivity, reading speed, microperimetry, optical coherence tomography and fundus photography. A questionnaire interview included assessment of vision-related QoL (Impact of Visual Impairment questionnaire), health status (EQ-5D), level of depressive symptoms (PHQ-9) and well-being (Warwick-Edinburgh Well-Being Scale). At baseline, the optimum multiple regression model accounted for 41% of the variance in vision-related QoL and included Mean Total Deviation or Mean Sensitivity with level of depressive symptoms. After 1 year, the optimum model to predict change in vision-related QoL accounted for 43% of the variance and included baseline contrast sensitivity and change in health status and reading speed. The most clinically useful measures of visual function, in identifying those with a reduced QoL or those at risk of a reduced QoL were contrast sensitivity, microperimetry, and reading speed. These outcomes may allow a better understanding of vision-related QoL if they were adopted in a clinical setting. In conclusion, the studies provide sufficient evidence to encourage a review of the clinical outcome measures most relevant to vision-related QoL

Visual pigment concentration and photoreceptor outer segment length in the human retina

Purpose: The Beer–Lambert law suggests that visual pigment optical density (OD) should be linearly related to the length of photoreceptor outer segments (POSs). Mammalian studies indicate that visual pigment concentration increases with POS length, but the nature of this relationship may vary due to factors such as visual pigment packing density or retinal eccentricity, and may not necessarily be linearly related. The purpose of this study was to establish the relationship between OD and POS length in humans. Methods: Spectral domain optical coherence tomography (OCT) was used to image POS, and imaging retinal densitometry (IRD) was used to measure OD at corresponding locations in 19 healthy participants (age range 25–82 years). POS length and OD measurements were extracted from OCT and IRD images at 23 discrete locations spanning the central 9° of the retina. The averaged data from all participants were fitted with models based on the Beer–Lambert law to establish the relationship between OD and POS length. Results: Visual pigment OD increased monotonically with POS length, but the relationship was non‐linear, and a straight‐line fit, based on a simple interpretation of the Beer–Lambert law, provided a poor description. A model allowing for different rod and cone visual pigment concentrations provided a superior fit. Specifically, the data were well described by a model where the molar concentration of visual pigment in cones and rods were 3.8 × 10−3 mol/L and 1.8 × 10−3mol/L, respectively. Conclusions: In accordance with the Beer–Lambert law, the results indicate that OD increases monotonically with POS length in humans, but the precise relationship is dependent on photoreceptor type. These results suggest that visual pigment concentration in rods is only about 48% of that found in cones. This may be due to the ubiquitous nature of artificial light that works to reduce the concentration of rhodopsin in rod photoreceptors

Automated Retinal Layer Segmentation Using Spectral Domain Optical Coherence Tomography: Evaluation of Inter-Session Repeatability and Agreement between Devices

Retinal and intra-retinal layer thicknesses are routinely generated from optical coherence tomography (OCT) images, but on-board software capabilities and image scaling assumptions are not consistent across devices. This study evaluates the device-independent Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) for automated intra-retinal layer segmentation and image scaling for three OCT systems. Healthy participants (n = 25) underwent macular volume scans using a Cirrus HD-OCT (Zeiss), 3D-OCT 1000 (Topcon), and a non-commercial long-wavelength (1040nm) OCT on two occasions. Mean thickness of 10 intra-retinal layers was measured in three ETDRS subfields (fovea, inner ring and outer ring) using the Iowa Reference Algorithms. Where available, total retinal thicknesses were measured using on-board software. Measured axial eye length (AEL)-dependent scaling was used throughout, with a comparison made to the system-specific fixed-AEL scaling. Inter-session repeatability and agreement between OCT systems and segmentation methods was assessed. Inter-session coefficient of repeatability (CoR) for the foveal subfield total retinal thickness was 3.43μm, 4.76μm, and 5.98μm for the Zeiss, Topcon, and long-wavelength images respectively. For the commercial software, CoR was 4.63μm (Zeiss) and 7.63μm (Topcon). The Iowa Reference Algorithms demonstrated higher repeatability than the on-board software and, in addition, reliably segmented all 10 intra-retinal layers. With fixed-AEL scaling, the algorithm produced significantly different thickness values for the three OCT devices (P<0.05), with these discrepancies generally characterized by an overall offset (bias) and correlations with axial eye length for the foveal subfield and outer ring (P<0.05). This correlation was reduced to an insignificant level in all cases when AEL-dependent scaling was used. Overall, the Iowa Reference Algorithms are viable for clinical and research use in healthy eyes imaged with these devices, however ocular biometry is required for accurate quantification of OCT images

The use of microperimetry in assessing visual function in age-related macular degeneration

Microperimetry is a novel technique for assessing visual function and appears particularly suitable for age-related macular degeneration (AMD). Compared to standard automated perimetry (SAP), microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye tracking system to correct the stimulus location for fixation loss and identifies any preferred retinal loci. A systematic review of microperimetry in the assessment of visual function in AMD identified 680 articles; of these, 52 met the inclusion criteria. Microperimetry and AMD is discussed in relation to: disease severity; structural imaging outcomes; other measures of visual function; and evaluation of the efficacy of surgical and/ or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone (EZ) band and retinal pigment epithelium (RPE) are clearly associated with reduced differential light sensitivity (DLS) despite the maintenance of good visual acuity (VA). Reduced DLS is also associated with outer segment thinning and RPE thickening in early AMD and with both a thickening and a thinning of the whole retina in CNV. However, microperimetry lacks the robust diffuse and focal loss age-corrected probability analyses associated with SAP and the technique is currently limited by this omission

Microperimetry in age-related macular degeneration: an evidence-base for Pattern Deviation probability analysis in microperimetry

Purpose: The “traffic light” color designation of differential light sensitivity used in a number of microperimeters does not encompass the conventional Total and Pattern Deviation probability analyses adopted by standard automated perimetry. We determined whether the color designation is indicative of abnormality as represented by the “gold standard” Pattern Deviation probability analysis. Methods: Total and Pattern Deviation probability levels, using two different methods, were derived at each of 40 stimulus locations, within 7° eccentricity, from 66 ocular healthy individuals (66 eyes) who had undergone microperimetry with the Macular Integrity Assessment microperimeter. The probability levels were applied to the corresponding fields from each of 45 individuals (45 eyes) with age-related macular degeneration (AMD) and evaluated in relation to the color designation. Results: Sensitivities designated in orange encompassed the entire range of Pattern Deviation probability levels (from normal to P ≤ 1%). Those designated in green were mostly normal; those in red/black generally corresponded to the ≤1% probability level. Conclusions: The green and the red/black designations are generally indicative of normal and abnormal probability values, respectively. The orange designation encompassed all probability outcomes and should not be relied upon for visual field interpretation. The evidence base indicates replacement of the color designation of sensitivity in AMD by Total Deviation and Pattern Deviation analyses. Translational Relevance: The use of Total and Pattern Deviation probability analyses is not universal in all microperimeters, and the derivation of these values indicates that color coding will lead to errors in evaluating visual field loss

Producing interventions for AIDS-affected young people in Lesotho's schools: Scalar relations and power differentials

This is the post-print version of the final paper published in Geoforum. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2009 Elsevier B.V.Children and youth are a key target group for interventions to address southern Africa’s AIDS pandemic. Such interventions are frequently implemented through schools, and are often complex products of negotiation between a range of institutional actors including international agencies, NGOs, government departments and individual schools. These institutions not only stand in different (horizontally scaled) spatial relationships to students in schools; they also appear to operate at different hierarchical levels. Empirical research with policy makers and practitioners in Lesotho, however, reveals how interventions are produced through flows of knowledge, funding and personnel within and between institutions that make it difficult to assert that any intervention is manifestly more international or more local than any other. Scale theory offers the metaphor of a network or web which usefully serves to move attention away from discrete organisations, sectors and scalar positionings and onto the relationships and flows between them. Nevertheless, organisations and development interventions are often partly structured in scalar hierarchical ways that express substantive power differentials and shape the forms of interaction that take place, albeit not binding them to strict binaries or nested hierarchies. A modified network metaphor is useful in aiding understanding of how particular interventions are produced through intermeshing scales and diverse fluid interactions, and why they take the form they do.RGS-IB

Comparison of inter-session repeatability for the two segmentation methods.

<p>Coefficients of repeatability for segmentation by the Iowa Reference Algorithms and on-board software are shown for the Topcon (left) and Zeiss (right) systems. The ‘equivalent retinal thickness’ values from the Iowa Reference Algorithms were used in this analysis.</p

Inter-session repeatability of the Iowa Reference Algorithms.

<p>Coefficients of repeatability (μm; and percentage) of mean retinal thickness produced by the Iowa Reference Algorithms at session 1 and session 2.</p

Intra-retinal layer thickness and CoR.

<p>Mean thickness of 10 intra-retinal layers segmented by the Iowa Reference Algorithms at session 1, on images from all three OCT devices. Error bars and table values represent inter-session CoR (μm) for each layer.</p

Correlation of retinal thickness differences against AEL.

<p>Difference in retinal thickness measurements (μm) versus axial eye length (mm) for the foveal subfield, as produced by the Iowa Reference Algorithms using two different transverse scaling methods.</p