Perimetry and AMD

1.4.2.1 Standard Perimetry and AMD

Several studies have examined the central visual field in AMD using a Humphrey Field Analyser (Atchison et al. 1990; Cheng & Vingrys 1993; Feigl et al. 2005; Frennesson et al. 1995; Midena et al. 1994,1997; Tolentino et al. 1994). All of these studies analysed as the main outcome, global mean sensitivity (MS) and in some cases, its standard

deviation. Other global indices, such as the mean deviation (MD) and probability analyses were not calculated, even when a large range of ages among the sample was present. One exception to this was a study which used number of defects from normal in a 16 point 6° by 4° stimulus grid (Tolentino et al. 1994).

Midena et al. (1994, 1997) found reduced sensitivity in the HFA 10-2 field in patients with early AMD, when fundi were graded using the International Classification System, in groups comprising approximately 30 patients. In eyes with drusen, MS was significantly lower in eyes with soft drusen compared to eyes without soft drusen, and in eyes with drusen larger than 63µm compared to eyes with drusen smaller than 63µm (Midena et al. 1994). A later study by the same group found significantly lower MS in patients, compared to age-matched controls (Midena et al. 1997). MS showed no significant differences with number of drusen (Midena et al. 1994, 1997). A progressive decrease in sensitivity was noticed with increased confluence of drusen, however, MS was unaffected by neither the presence of focal hyperpigmentation, nor RPE atrophy (Midena et al. 1997). The findings of these two studies has less impact when it is considered that where significant differences in MS were found, they were of very small magnitudes, of 1 to 2dB.

Cheng & Vingrys (1993) also discovered that patients with early AMD exhibited reduced mean sensitivities on the HFA 10-2 test compared to age-matched normal subjects, although this was not statistically significant. Most of the defects detected were in the parafovea, at 5° to 10°. In contrast to this, Atchison et al. (1990) compared HFA 10-2 and 24-2 fields in 15 subjects with drusen and pigmentary changes to 15 age-matched normals and reported no significant difference between the two groups. Similarly, Frenesson et al. (1995) discovered normal 10-2 central visual fields in 27 subjects with pigmentary changes and soft drusen, some of which were confluent. Feigl et al. (2005) reported that 10-2 MS was within normal limits in thirteen patients with early AMD, graded using the AREDS grading system. This was not significantly

different from thirteen age-matched normal subjects, at baseline and one year after baseline (Feigl et al. 2005). Tolentino et al. (1994) detected that reduced sensitivity and drusen area were not significantly correlated, but sensitivity was reduced significantly with increased RPE atrophy.

Earlier studies involving a Friedmann Visual Field Analyser, an autoplot tangent screen (Swann & Lovie-Kitchin 1991) and a Goldmann perimeter using the static mode in the central 10° (Hart et al. 1983) have shown paracentral scotomata and preservation of central vision. Scanning laser ophthalmoscope (SLO) perimetry has been utilised to measure visual fields in AMD. The accuracy of fixation monitoring is improved over standard perimetry as correction can be made for loss of fixation. This advantage is evident as central visual field loss due to AMD is known to be associated with poorer fixation (Fujii et al. 2003). SLO perimetry is reviewed in section 1.4.3.1.

1.4.2.2 SWAP and AMD

Short-wavelength automated perimetry (SWAP) has been well documented in the early detection of glaucoma (Johnson et al. 1993b,c; Sample & Weinreb 1992). Glaucomatous progression was detected three to four years earlier in SWAP than in standard perimetry (Johnson et al. 1993b,c). SWAP also offered improved detection of focal defects in diabetic macular oedema, than standard perimetry (Hudson et al. 1998, Remky et al. 2000). Clinically, the use of SWAP did not become widespread following these findings, due to its greater variability in the 30° field, compared to standard perimetry (Wild et al. 1998). However in the central 10°, SWAP has a flatter hill of vision and the between-subject variability of SWAP is significantly less than in the 30° field (Kwon et al. 1998; Wild et al. 1998). This allows for a more accurate statistical interpretation using standard perimetric methodology and greater capability in the detection of focal loss (Cubbidge et al. 2002). It is known that patients with AMD have a diminished short-wavelength sensitive cone mechanism sensitivity (Chapter 1.4.2.3).

The number of studies documenting the measurement of SWAP in AMD is scarce (Remky et al. 2001b; Remky & Elsner 2005).

In 126 patients with early AMD, 75 of which had late AMD in the fellow eye, central 10° field SWAP was performed, using a HFA (Remky et al. 2001b). A decline in MS with age was found. In eyes of equal age and LogMAR acuity, those with soft drusen had significantly decreased MS compared to eyes without. Fellow eyes of eyes with exudative AMD had lower sensitivities compared to patients without exudative disease. Focal pigmentation was found to be related to an eccentricity effect. Eyes with hyperpigmentation had reduced sensitivity centrally compared to peripherally and the opposite was true for eyes without hyperpigmentation. The authors quoted SWAP sensitivity loss as a risk factor of AMD, although standard visual field data was not collected in their study (Remky et al. 2001b).

Another blue-on-yellow perimetry technique, using a scanning laser ophthalmoscope, has been employed to study early AMD (Remky & Elsner 2005). Reduced sensitivity in a 10° rectangular stimulus configuration consisting of 16 stimuli was recorded in 24 early AMD patients and age-matched controls. Patients with soft drusen were found to have lower MS values and higher between-subject variation than those with hard drusen. Areas of drusen, atrophic patches, and hyperpigmentation had lower sensitivity than areas without, thus showing focal loss in addition to the diffuse loss (Remky & Elsner 2005).

1.4.2.3 Short-Wavelength Sensitive Cone Pathway Sensitivity

The decline in sensitivity with age in SWAP is approximately 15dB per decade (Johnson et al. 1988a). Other psychophysical tests have determined an age-related loss of the short-wavelength sensitive cone pathway sensitivity at the fovea (Eisner et al. 1987a; Werner & Steele 1988).

Investigators have observed diminished short-wavelength sensitive cone pathway sensitivity in patients with AMD (Eisner et al. 1987b; Haegerstrom-Portnoy et al. 1989).

Eisner et al. (1987a,b, 1991, 1992) employed a two-channel Maxwellian view testing device, where isolation of the short-wavelength sensitive pathway was achieved using small stimuli, 3° and 1° in diameter of wavelength 440nm upon a 6° chromatic background of wavelength 580nm. A 20Hz square wave flickering stimulus was used to determine threshold sensitivity (Eisner et al. 1987a,b, 1991, 1992). A significantly lower sensitivity was ascertained in fellow eyes of patients with CNV, which had drusen, with and without hyperpigmentation, compared to an age-matched normal group (Eisner et al. 1987b). Using similar instrumentation, but differing stimulus conditions (440nm and 480nm, 2° stimulus on a 20° field, which flickered at 25Hz), patients with drusen and pigmentary changes had significant sensitivity loss and greater variability around the measure compared to control subjects (Haegerstrom- Portnoy et al. 1989). By contrast, within the same study, sensitivity in another patient group, who had less extensive retinal changes and good visual acuities, did not significantly differ from control subjects.

Low foveal short-wavelength sensitive cone pathway sensitivities were found to predict the development of exudative changes in fellow eyes of exudative disease followed over 18 months (Eisner et al. 1992). In fellow eyes of exudative disease with good acuity, eyes with any of the high risk features, focal hyperpigmentation, more than minimal confluence of drusen and large drusen; had significantly lower short- wavelength sensitive cone pathway sensitivity than low risk eyes without these features (Eisner et al. 1991). A modified Tübinger perimeter was employed to measure foveal short-wavelength sensitive cone pathway sensitivity using a flickering 2° blue stimulus, 450nm on a yellow chromatic background of 578nm, and a correction for lens density and macular pigment was included (Sunness et al. 1989). A weak correlation between high risk drusen, defined as soft drusen, confluence of drusen or hyperpigmentation and decreased sensitivity was illustrated (Sunness et al. 1989). In this study, Sunness et al. (1989) highlighted a predictive ability of reduced short-wavelength sensitive cone

pathway sensitivity based on its appearance in advance of clinical detection. Another two-channel Maxwellian view system using a 1° flickering stimulus on 9° circular chromatic background isolated short, medium and long wavelength sensitive cones using various filters, revealed loss of sensitivity in the short-wavelength cones alone, in both exudative and non-exudative disease, in a small sample of three subjects (Applegate et al. 1987).

Beirne et al. (2006) investigated the relationship between short-wavelength sensitive grating acuity and severity of stage of early AMD. Fundus photographs were graded by the Wisconsin grading system and staged according to the definitions used in the Rotterdam Eye Study. Resolution acuity was found to be reduced in eyes with AMD, however there was no direct relationship with increased disease stage.

It has been reported that normal elderly subjects who had high macular pigment density also had higher short-wavelength cone sensitivity than subjects with lower macular pigment density (Hammond et al. 1998). The study implied a protective role of macular pigment over visual sensitivity.

1.4.3 Other Non-standard Perimetric Techniques and AMD