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Ординатура / Офтальмология / Английские материалы / Glaucoma An Open Window to Neurodegeneration and Neuroprotection_Nucci, Cerulli, Osborne_2008.pdf
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a very high spatial discrimination, whereas peripheral vision is much less defined. In order to preserve the foveal highly detailed vision, inter receptors connections are absent; this means that receptive fields have no overlapping. On the other hand, in the peripheral retina there is a high interconnection among receptors, intraretinal cells, and ganglion cells, leading to a partial overlapping of the contiguous receptive fields.

The concept of overlapping receptive fields is also known as redundancy. Due to redundancy, a single stimulus may simultaneously stimulate two or more RGCs; in the case of retinal damage, this guarantees a higher probability of the stimulus to be transmitted to the brain. As a consequence, the higher the redundancy, the more minor the probability of detection of early damages of the RGCs. It has been demonstrated that, apart from the foveal area, P-pathway is endowed with high redundancy (Johnson, 1994). On the other hand, it is likely that the receptive fields of a sparse subset of RGCs (such as M- and K-cells) have a lower overlap, though low redundancy has until now been demonstrated only for M-cells (Haymes et al., 2005).

FDT: rationale and perimetric techniques

FDT is based on a phenomenon described about 40 years ago by Kelly, who observed that when an achromatic sinusoidal grating of low spatial frequency undergoes counterphase flickering at a hightemporal frequency, the apparent spatial frequency of the grating appears to be doubled (Kelly, 1966). He reported that this ‘‘frequency-doubling’’ phenomenon occurred for sinusoidal gratings having a spatial frequency less than approximately 3 cyc/degree undergoing a counterphase flickering at a temporal frequency greater than 7 Hz.

The FDT stimulus predominantly stimulates the M-cell pathway, which is primarily involved in motion and flicker detection and represents about 10% of all RGCs. Some believe that the frequency-doubling illusion in humans is mediated by the subgroup of My cells (Maddess and Henry, 1992). However, the existence of M-cells that exhibit nonlinear response properties, My cells, is not universally agreed. White et al. (2002) reported

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that there is no evidence of a separate nonlinear M-cell class in the primate visual system. They suggested that a cortical loss of temporal phase discrimination is the principal cause of the illusion and proposed that the mechanisms underlying the illusion resemble those underlying the detection of full-field flicker, which appears to be accomplished through the M-cell pathway. Thus, FDT (and particularly Matrix FDT) is most likely a probe of contrast sensitivity: it does not depend on whether the stimulus is perceived as doubled but simply measures detection thresholds of the M-cell pathway.

FDT perimeter (Welch Allyn, Skaneateles Falls, NY; and Humphrey Instruments, San Leandro, CA) uses a vertical sine wave grating of low spatial frequency (0.25–0.50 cyc/degree) that undergoes counterphase flickering at a high-temporal frequency (12–25 Hz). The contrast of the stimulus is modified in each location to calculate threshold sensitivity.

FDT comprises firstand second-generation tests. The major difference between the two groups is the number of tested locations, the dimension, and the characteristics of the stimuli (Table 2); Fig. 1 shows the FDT tests most commonly used in glaucoma practice.

In the first-generation FDT, two programs are available: C-20 and N-30. C-20 consists of a grid of 16 square locations of 10 10 degrees each, projecting on the central 20 degrees of the retina, and a foveal circular grid location of 5 degrees. The N-30 program also tests two additional locations between 20 and 30 degrees of the nasal retina immediately above and below the horizontal line, for a total of 19 locations.

Two strategies are available: screening (suprathreshold) and full-threshold. Both can be performed using the C-20 or the N-30 programs. The average test duration is about 1–1.5 min for the screening test and 4–5 min for the full-threshold mode, and it is directly related to the presence of visual field defects. The greater the visual field loss, the longer the test duration.

The screening strategy compares the point-to- point results with an age-corrected normative database and assigns one of the following values: within normal limits (PX1%), mild relative loss

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Table 2. Features of the programs of the first-generation FDT (above) and the novel programs of Matrix FDT (bottom)

Program

C-20 screening

C-20 threshold

N-30 threshold

N-30 screening

 

 

 

 

 

Spatial frequency (cyc/degree)

0.25

0.25

0.25

0.25

Temporal frequency (Hz)

25

25

25

25

Stimulus size

101a

101a

101a

101a

Tested area

201

201

201 (301 nasally)

201 (301 nasally)

Number of tested locations

17

17

19

19

Test time (in normal subjects)

45 s

4 min

5 min

90 s

 

 

 

 

 

Program

24-2 threshold

30-2 threshold

10-2 threshold

Macula screening

 

 

 

 

 

Spatial frequency (cyc/degree)

0.5

0.5

0.5

0.5

Temporal frequency (Hz)

18

18

12

12

Stimulus size

51

51

21

21

Tested area

241 (301 nasally)

301

101

51

Number of tested locations

55

69

44

16

Test time (in normal subjects)

5 min

6 min

4 min

90 s

 

 

 

 

 

aThe size of the foveal stimulus is 51.

(Po1%), moderate relative loss (Po0.5%), and severe loss (point not seen; failure to respond to maximum contrast level). In the full-threshold strategy, point-to-point threshold is calculated using a Method of Binary Search (MOBS) procedure (Tyrell and Owens, 1998) that is a different threshold approach compared to the staircase procedure used in Humphrey-SAP. Then the threshold values are compared to the normative database; each location is deemed as normal (PW5%) or abnormal at different levels of probability (Po5%, o2%, o1%, o0.5%) in two maps: total deviation map and pattern deviation map. Point-to-point results are depicted on a colored scale corresponding to the different probability levels.

Reliability indices (fixation errors, false-positive and false-negative) are provided in both strategies. Similarly to the SAP programs with short duration and absence of short-term fluctuation (such as SITA-standard and SITA-FAST), full-threshold FDT also gives two global indices: mean defect (MD) and pattern standard deviation (PSD).

The FDT database contains data from more than 700 eyes of 450 normal subjects with ages ranging from 18 to 85. As it has been shown that FDT sensitivity is lower for the second tested eye versus the first (probably due to cortical

adaptation to the FDT stimulus), the machine automatically adjusts the values of the second eye.

The first FDT version has few manufacturing limitations: a system to monitor fixation throughout testing is unavailable (the operator cannot check whether the patient is fixating properly or pause the test to adjust patient alignment during the examination); in order to examine the two nasal points in the N-30 strategy, the fixation target is moved temporally, which may be confusing or cause improper fixation in some patients. FDT includes a small printer which can provide a brief printout; an external computer using specific software, Windows ViewFinder, is needed to obtain more detailed printouts and store data.

The second-generation FDT perimeters include a new program called Matrix which is very similar to the previous version except for the use of a smaller size of the stimulus (5 degrees for the 24-2 and the 30-2 programs and 2 degrees for the 10-2 program), a higher number of tested points, a more efficient method to calculate threshold, and a slightly longer duration (about 6 min). The programs of this FDT version are closer and more comparable to the same programs of SAP; other advantages are the presence of a video eye monitor to check patient alignment and cooperation during the test, a bigger screen to examine the nasal

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Fig. 1. Printouts of a C-20 screening test (a), an N-30 full-threshold test (b), and a 24-2 Matrix FDT (c).

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Fig. 1. (Continued).

targets within the central 301 without a moving fixation target, the possibility to store data on the machine, and an enhanced software for result interpretation. Matrix FDT interpretation is based on a database of 270 subjects with age ranging from 18 to 85.

SWAP: rationale and perimetric techniques

The evidence of a deficiency in color vision, particularly in the blue–yellow axis, has been

clearly demonstrated in patients affected by glaucoma more than 25 years ago (Drance et al., 1981). Information on the blue–yellow axis is projected to LGN by koniocells, which are a small subgroup of RGCs endowed with little redundancy, a fact which is supposed to allow early glaucoma detection.

The commercially available SWAP version is a modification of the SAP test obtained by Humphrey Field Analyzer (Humphrey-Zeiss, Dublin, CA) using a V stimulus (1.8 degree) of blue light at 440 nm projected to a background illuminated

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Fig. 2. Printout of a full-threshold SWAP.

with yellow light (570–590 nm) at a luminance of 200 cd/m2. The test can be performed over both the 30 and 24 central degrees of the retina; respectively, 76 and 54 locations are tested.

As evident in Fig. 2, SWAP tests are performed and analyzed similarly to SAP: reliability parameters (false-positive, false-negative, and fixation loss) and perimetric indices (MD; PSD; short fluctuation, SF; corrected PSD, CPSD) are calculated, gaze tracking is available and test duration is recorded; the point-to-point sensitivity is reported in decibel and greytone maps (the latter

of which should be ignored; it is usually misleading because it is calibrated on SAP sensitivities, which are higher than SWAP). Point-to-point sensitivities are matched to those of normal subjects of the same age in order to identify diffuse (total deviation map) and localized (pattern deviation map) defects. A glaucoma hemifield test (GHT) is finally performed by comparison of symmetric areas of the superior and inferior hemifields.

The full-threshold strategy is the most commonly used but it has a long duration (up to 20 min per eye) and, as a consequence, a high