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1.5.1.1 Visual acuity

Visual acuity (VA) remains the principal functional measure used to monitor AMD disease progression in clinical practice and it requires detection, resolution and recognition of a target. As detection and resolution are measurements of macular function, VA is often affected in late AMD, however, other aspects of retinal function are compromised before this change is seen (Lovie-Kitchin and Feigl 2005). The same size AMD lesions can result in varying losses of VA, (Neelam et al. 2009) making it an unreliable diagnostic tool, or indicator of disease progression. Depending on the size and position of the resulting scotoma, VA can still be good even when a subject is struggling, for example, with reading (Sarks et al. 1988). In 173 eyes diagnosed with late AMD it was found that 71.7% had a

reasonable recorded VA of 6/9-6/12 (Vinding 1990), and although Klein et al. (1995) found that late AMD did cause a reduction in VA of 7 lines, they also agreed that other measures of visual function may be more sensitive in detecting AMD.

1.5.1.2 Amsler chart

Self-monitoring is important for the timely detection of progression and successful treatment of nAMD (Trevino 2008). The Amsler grid (Amsler 1953) is given to patients at risk of developing nAMD for this purpose, and is designed to detect scotomas and

metamorphopisa. Subtending 20⁰ at 30 cm, the chart uses a grid pattern composed of 1⁰ squares, with the patient asked to report any metamorphopsia (perceived distortions) or scotomas (gaps in the chart) whilst looking at a central fixation dot. However studies have suggested that patients are failing to notice these changes, with 77% of scotomas of 6⁰ diameter or less not being detected by Amsler testing (Schuchard 1993). These failings may be due to poor patient understanding of the test (Trevino 2008), poor or eccentric fixation (Loewenstein 2007) or due to a filling in effect (Crossland and Rubin 2007). Other self-monitoring methods, including Preferential Hyperacuity Perimetry (Crossland et al. 2007; Trevino 2008) and Macular Mapping (Trevino 2008) are currently under

investigation.

1.5.1.3 Perimetry

Perimetry is a subjective technique that assesses the topographical sensitivity of the visual field. Accurate visual field assessment relies on central fixation, which is difficult for

patients with advanced AMD, however, certain perimetric techniques have been shown to be sensitive to AMD (Acton et al. 2012a).

Flicker perimetry measures the contrast threshold for a stimulus presented at a fixed temporal frequency. Flickering targets have been shown to be sensitive to GA progression and to monitoring AMD (Mayer et al. 1994; Phipps et al. 2004), being more sensitive than static perimetric targets (Phipps et al. 2004). They can also be used to predict progression from early to late AMD (Luu et al. 2012). Frequency doubling perimetry (FDT) measures the contrast sensitivity for a grating of fixed temporal frequency to assess the visual field. The short testing time and independence of results from pupil size makes this test

attractive in AMD assessment. However, it has limited use in the functional evaluation of AMD due to its insensitivity in the detection of small AMD lesions (Sheu et al. 2002). It can, though, provide information about the size and depth of an area of sensitivity loss that correlates with reading speed in AMD (Anderson et al. 2011).

Short wavelength automated perimetry (SWAP) preferentially measures s-cone mediated thresholds. In the detection of AMD, VA has been found to better differentiate between people with AMD and those without than SWAP. Age-related macular degeneration lesions found with SWAP perimetry have been found to be greater in area and depth when compared to standard automated perimetry (Acton et al. 2012a). A correlation between lower SWAP sensitivity and soft drusen (Remky et al. 2001) has also been reported.

Microperimetry assesses the visual function of a specific area of the retina and correlates it with a fundus image, giving a comparison of structure and function. It can rapidly assess early vision loss in AMD (Dinc et al. 2008) and may be a useful tool in the detection and monitoring of AMD (Querques et al. 2008; Midena et al. 2007). A significant correlation has been found between reduced retinal sensitivity and drusen volume (Hartmann et al. 2011) and between field defects and a significant thinning of the outer segment

associated with photoreceptor loss (Acton et al. 2012b).

1.5.1.4 Contrast sensitivity

Visual acuity measures the highest spatial frequency at which a high contrast target can be seen. An image, however, is made up of many different contrasts and spatial

frequencies, so a contrast sensitivity assessment provides a comprehensive overview of an individual’s spatial visual function. Contrast sensitivity is affected by many factors including light levels, eccentricity, hypoxia and age, reducing with normal ageing (Owsley 2011). Contrast sensitivity losses have been found to precede changes in VA in patients with early AMD (Stangos et al. 1995; Midena et al. 1997) GA, (Sunness et al. 1997) and with the increased sub retinal tissue volume seen in nAMD (Keane et al. 2010). It has been suggested that contrast sensitivity should be included as an outcome measure in the assessment of treatments for nAMD as it may show an improvement in visual function after treatment when VA does not (Monés and Rubin 2005; Rubin and Bressler 2002).

1.5.1.5 Colour vision

Tritan (blue-yellow) colour vision defects have been found in people with early and advanced AMD (Feigl et al. 2005b; Cheng and Vingrys 1993; Holz et al. 1995; Arden and Wolf, 2004; Dimitrov et al. 2011), which is possibly due to a reduction in S-cone sensitivity (Eisner et al. 1992). However this is not a universal finding in early AMD, possibly due to the changes being too subtle to respond to testing (Midena et al. 1997). A study by O’Neill-Biba et al. (2010) found that both tritan and red-green defects could be used as a sensitive measure of functional change in AMD.