Perceptual learning in patients with macular degeneration

Chapter 51 - Nonsensory Signals in Early Visual Cortex

Patients with age-related macular degeneration (AMD) are reliant on their peripheral visual field. Oculomotor training can help them to find the best area on intact peripheral retina and to efficiently stabilize eccentric fixation. In this study, nine patients with AMD were trained over a period of 6 months using oculomotor training protocols to improve fixation stability. They were followed over an additional period of 6 months, where they completed an auditory memory training as a sham training. In this cross-over design five patients started with the sham training and four with the oculomotor training. Seven healthy age-matched subjects, who did not take part in any training procedure, served as controls. During the 6 months of training the AMD subjects and the control group took part in three functional and structural magnetic resonance imaging (MRI) sessions to assess training-related changes in the brain function and structure. The sham-training phase was accompanied by two more fMRI measurements, resulting in five MRI sessions at intervals of 3 months for all participants. Despite substantial variability in the training effects, on average, AMD patients benefited from the training measurements as indexed by significant improvements in their fixation stability, visual acuity, and reading speed. The patients showed a significant positive correlation between brain activation changes and improvements in fixation stability in the visual cortex during training. These correlations were less pronounced on the long-term after training had ceased. We also found a significant increase in gray and white matter in the posterior cerebellum after training in the patient group. Our results show that functional and structural brain changes can be associated, at least on the short-term, with benefits of oculomotor and/or reading training in patients with central scotomata resulting from AMD.

Neural and perceptual adaptations in bilateral macular degeneration: an integrative review.

Subjects with bilateral central vision loss (CVL) use a retinal region called the preferred retinal locus (PRL) for performing various visual tasks. We probed the fixation PRL in individuals with bilateral macular disease, including age-related macular degeneration (AMD) and Stargardt disease (STGD), for localized sensitivity deficits. Three letter words at the critical print size were presented in the NIDEK MP-1 microperimeter to determine the fixation PRL and its radial retinal eccentricity from the residual fovea in 29 subjects with bilateral CVL. Fixation stability was defined as the median bivariate contour ellipse area (BCEA) from 3 fixation assessments. A standard 10-2 grid (68 locations, 2° apart) was used to determine central retinal sensitivity for Goldmann size II test spots. Baseline and follow-up supra-threshold screening of the fixation PRL for localized sensitivity deficits was performed using high density (0.2° or 0.3° apart) 0dB Goldmann size II test spots. Custom MATLAB code and a dual bootstrapping algorithm were used to register test-spot locations from the baseline and follow-up tests. Locations where the 0dB test spots were not seen on either test were labeled as micro-scotomas (MSs). Median BCEA correlated poorly with the radial eccentricity of the fixation PRL. Mean (±SD) sensitivity around the PRL from 10-2 testing was 4.93±4.73dB. The average percentage of MSs was similar for patients with AMD (25.4%), STGD (20.3%), and other etiologies of CVL (27.1%). The fixation PRL in subjects with bilateral CVL frequently includes local regions of sensitivity loss.

Older individuals with macular diseases, such as age-related macular degeneration, experience central vision loss (CVL) due to degeneration of their photoreceptors and retinal cells. Patients with CVL may experience various vision impairments, including of visual acuity, fixation stability, contrast sensitivity, and stereoacuity. After CVL, most patients develop a preferred retinal locus outside the affected macular region, which serves as a new visual reference. In this review, we provide an overview of the visual function and impairment in individuals with CVL. In addition, the important role of biofeedback training on the visual function and activity of individuals with CVL is also reviewed. Accordingly, the location and development of the preferred retinal loci are discussed. Finally, this review discusses how to conduct biofeedback training to treat individuals with CVL.

Many persons with low vision have diseases that damage the retina only in selected areas, which can lead to scotomas (blind spots) in perception. The most frequent of these diseases is age-related macular degeneration (AMD), in which foveal vision is often impaired by a central scotoma that impairs vision of fine detail and causes problems with reading and recognizing faces. One would think that differences between damaged and relatively intact areas should be painfully obvious to those who have AMD. However, as clinical practice and scientific studies have shown, this is often not the case (Safran & Landis, 1996, 1999; Schuchard, 1995). Thus, patients and rehabilitation workers need to know where on the retina or in the visual field vision is still good enough to be usable. Having this information increases the chances for successful rehabilitation, the necessity and feasibility of which have been demonstrated (Backman & Inde, 1979; Nilsson, Frennesson, & Nilsson, 2003; Otto, 1969; Park, 1999). The fact that rehabilitation is possible emphasizes the need for a topographic assessment of remaining vision. In this article, I describe the Macular Mapping Test (MMT) and illustrate with case reports how it can be used in clinical practice to assist in the assessment and rehabilitation of patients with central vision loss. THE IDEAL SOLUTION Topographic assessment is best done by a scanning laser ophthalmoscope (SLO) that shows live images of the retina and the stimulus that is scanned directly onto it. A useful vision assessment in AMD does not need to encompass the entire visual field. It can be restricted to the macula, a central area of 20 degrees diameter, where most preferred retinal loci (PRL) develop (Fletcher & Schuchard, 1997). If small spots of light are flashed onto the retina (microperimetry), the patient indicates which are detected and which are not. For precise placement of stimuli, modern software compensates for involuntary eye movements during testing, so that precise fixation is not necessary (MacKeben & Gofen, 2007). Since SLOs are expensive and rare, they are not available to most vision professionals. WHAT OTHER MEANS ARE AVAILABLE? Conventional perimetry can provide relevant data, but it is time-consuming and requires sophisticated equipment and special expertise. In addition, the resulting intensity thresholds are not needed to find usable remaining vision for rehabilitation. The standard tangent screen test has shortcomings in that it makes it hard to include a discrimination (recognition) paradigm for a better measurement of visual performance. Furthermore, it is difficult to time the appearance and disappearance of a target precisely at defined locations, and the results can vary with the examiner's level of skill and personal habits. The Amsler grid is a subjective test that is sensitive only to drastic changes, but not to those that develop over longer periods. At best, it indicates where damage has been done, but not visual performance. In addition, the normal filling-in mechanism often prevents the detection of scotomas of less than 5 degrees diameter (Ramachandran & Gregory, 1991; Schuchard, 1993). [FIGURE 1 OMITTED] Note that measuring visual acuity alone is insufficient, despite the importance of visual acuity for prescribing optical aids, because it has limited utility in predicting the performance of activities of daily living, like reading (Backman, 2000; Crossland, Culham, & Rubin, 2005) or visually guided mobility (Brown, Brabyn, Welch, Haegerstrom-Portnoy, & Colenbrander, 1986; Hassan, Lovie-Kitchen, & Woods, 2002; Marron & Bailey, 1982) after the loss of central vision. Also note that subsets of the data presented here were published previously (MacKeben & Colenbrander, 2000; MacKeben, Colenbrander, & Gofen, 1999). DESCRIPTION OF THE TEST Procedure Although MMT is not new (MacKeben & Colenbrander, 2000; MacKeben et al. …

Objective To investigate the distribution of the preferred retinal locus (PRL) of eccentric fixation in eyes with high myopia. Methods A total of 40 highly myopic patients (54 eyes) with eccentric fixation were examined by MP-1 microperimeter to identify the PRL. The position of PRL relative to the fovea was estimated using the 90% confidence ellipse of normal adult foveal fixation. The differences of visual acuity between desirable and PRL were tested by analysis of variance. Results In 54 eyes with high myopia, 24 eyes (44.44%) had PRL of eccentric fixation below the scotoma after loss of central vision; 19 eyes (35.19%) had a left-field PRL; 6 eyes (11.11%) had an upper-field PRL; and 5 eyes (9.26%) had right-field PRL. In 14 patients who had binocular eccentric fixation, 13 had the same fixation pattern in both eyes, including lower-field PRL in 7 (50.00 %), left-field PRL in 5 (35.71 %), and upper-field PRL in 1 patient (7.14%). The difference of visual acuity between lower- and left-field PRL group and right- and upper-field undesirable PRL group was not statistically significant (F=0.144, P > 0.05). Conclusions The eccentric fixation in eyes with high myopia is usually situated as near as possible to the fovea. The optimal PRL is inferior visual field. Key words: Myopia; degenerative/complications; Fixation; ocular/pathophysiology; Perimetry

Apparent motion (AM) is induced when two stationary visual stimuli are presented in alternating sequence. Intriguingly, AM leads to an impaired detectability of stimuli along the AM path (i.e., AM-induced...

Objective: Preferred retinal locus (PRL) training has been applied to low-vision rehabilitation for patients with central vision loss (CVL). This study aimed to explore the characteristics of a natural PRL in eyes with different macular lesions. The data may be useful in customizing training programs. Methods: A total of 72 eyes with CVL were included and assigned into two groups. In group A, 29 eyes diagnosed with macular holes featured relatively sharp borders and small areas of lesions. In group B, 44 eyes showed lesions characterized by irregular borders and large areas. The PRL location relative to a scotoma in the retina, fixation stability, and the average threshold surrounding the PRL were determined and compared between the two groups. Results: In group A, the PRL was located above in 48.28%, below in 27.59%, left in 62.07%, right in 31.03%, and inside in 3.45% of the eyes. In group B, the PRL was located above in 39.53%, below in 4.65%, left in 44.19%, right in 6.98%, and inside in 27.91% of eyes. The amount of retinal displacement occurring within 1° from an initial reference point (P< .05) and the 95% bivariate contour ellipse area (P< .05) in group A were respectively higher and lower than those in group B. However, the average thresholds around the PRLs in the two groups showed no significant difference (P > .05). Conclusions: A PRL to the left of or above a scotoma tends to develop to avoid the right and inferior field defect, regardless of the scale and boundary of lesions. Although light sensitivity around a PRL shows no relation to lesion features, fixation stability is worse in irregular and large lesions.

Attention can dramatically enhance behavioral performance based on a visual stimulus, but the degree to which attention modulates activity in early visual cortex is unclear. Whereas single-unit studies of spatial attention in monkeys have repeatedly revealed relatively modest attentional modulations in V1, human functional magnetic resonance imaging studies demonstrate a large attentional enhancement of the blood oxygen level-dependent (BOLD) signal in V1. To explore this discrepancy, we used intracranial electrodes to directly measure the effect of spatial attention on the responses of neurons near the human occipital pole. We found that spatial attention does not robustly modulate stimulus-driven local field potentials in early human visual cortex, but instead produces modest modulations that are consistent with those seen in monkey neurophysiology experiments. This finding suggests that the neuronal activity that underlies visual attention in humans is similar to that found in other primates and that behavioral state may alter the linear relationship between neuronal activity and BOLD.

During smooth pursuit, the image of the target is stabilized on the fovea, implying that speed judgments made during pursuit must rely on an extraretinal signal providing precise eye speed information. To characterize the introduction of such extraretinal signal into the human visual system, we performed a factorial, functional magnetic resonance imaging experiment, in which we manipulated the factor eye movement, with "fixation" and "pursuit" as levels, and the factor task, with "speed" and "form" judgments as levels. We hypothesized that the extraretinal speed signal is reflected as an interaction between speed judgments and pursuit. Random effects analysis yielded an interaction only in dorsal early visual cortex. Retinotopic mapping localized this interaction on the horizontal meridian (HM) between dorsal areas visual 2 and 3 (V2/V3) at 1-2 degrees azimuth. This corresponded to the position the pursuit target would have reached, if moving retinotopically, at the time of the subject's speed judgment. Because the 2 V2/V3 HMs are redundant, both may be involved in speed judgments, the ventral one involving judgments based on retinal motion and the dorsal one judgments requiring an internal signal. These results indicate that an extraretinal speed signal is injected into early visual cortex during pursuit.

The effect of focal visual attention on backward pattern masking was investigated using an orientation discrimination task. The results show that attention reduces primarily the effect of interruption masking, the later component of pattern masking, which occurs when the delay between the target and mask onset is about 50-150 ms. The strongest spatial cueing effect, i.e. the strongest reduction of the orientation discrimination threshold due to focal attention, was observed at intermediate (approximately 100 ms) target-to-mask stimulus onset asynchrony (SOA). There was a weak effect of cueing at shorter SOAs, and no or a very weak attentional effect was present at longer target-to-mask SOAs, where the pattern masking effect is absent. The dynamics of attentional modulation of backward pattern masking correlates closely with the dynamics of the attentional modulation of neuronal responses in the early visual cortex.

Disorders that specifically affect central and peripheral vision constitute invaluable models to study how the human brain adapts to visual deafferentation. We explored cortical changes after the loss of central or peripheral vision. Cortical thickness (CoTks) and resting-state cortical entropy (rs-CoEn), as a surrogate for neural and synaptic complexity, were extracted in 12 Stargardt macular dystrophy, 12 retinitis pigmentosa (tunnel vision stage), and 14 normally sighted subjects. When compared to controls, both groups with visual loss exhibited decreased CoTks in dorsal area V3d. Peripheral visual field loss also showed a specific CoTks decrease in early visual cortex and ventral area V4, while central visual field loss in dorsal area V3A. Only central visual field loss exhibited increased CoEn in LO-2 area and FG1. Current results revealed biomarkers of brain plasticity within the dorsal and the ventral visual streams following central and peripheral visual field defects.

Purpose:Hereditary macular dystrophies (HMD) result in early onset central field loss. Evidence for cortical plasticity has been found in HMD, which may enhance peripheral visual abilities to meet the increased demands and reliance on the peripheral field, as has been found in congenitally deaf adults and habitual action video-game players. This is a qualitative synthesis of the literature on the effect of early onset central field loss on peripheral visual abilities. The knowledge gained may help in developing rehabilitative strategies that enable optimisation of remaining peripheral vision.Methods:A systematic search performed on the Web of Science and PubMED databases yielded 728 records published between 1809 to 2020, of which seven case-control studies were eligible for qualitative synthesis.Results:The search highlighted an overall paucity of literature, which lacked validity due to small heterogeneous samples and deficiencies in reporting of methods and population characteristics. A range of peripheral visual abilities at different eccentricities were studied. Superior performance of HMD observers in the peripheral field or similarities between the preferred retinal loci (PRL) and normal fovea were observed in four of seven studies. Findings were often based on studies including a single observer. Further larger rigorous studies are required in this area.Conclusions:Spontaneous perceptual learning through reliance on and repeated use of the peripheral field and PRL may result in some specific superior peripheral visual abilities. However, worse performance in some tasks could reflect unexpected rod disease, lack of intensive training, or persistent limitations due to the need for cones for specific tasks. Perceptual learning through training regimes could enable patients to optimise use of the PRL and remaining peripheral vision. However, further studies are needed to design optimal training regimes.

Perifoveal laser photocoagulation has been proposed for the treatment of subfoveal neovascular membranes in age-related macular degeneration. We evaluated residual function in seven eyes of six treated patients by means of transient focal visual potentials evoked with a scanning laser ophthalmoscope. The site of the preferred retinal locus was determined. The modulation of the helium-neon laser beam generated three tests (a homogeneous 6 x 6 degrees square--offset and onset--and two alternating pattern checkerboards 6 x 6 degrees and 2.5 x 2.5 degrees 60', 2 Hz) projected onto the preferred retinal locus. The focal visual evoked potentials were recorded. One eye had an unstable fixation with no discernible focal visual evoked potentials. The other six eyes had a stable fixation located in the superior retina, temporally for the right eyes and nasally for the left eyes. The homogeneous 6 x 6 degrees square evoked discernible responses in all six patients. The two checkerboards evoked discernible responses in five of six patients. These results were compared with those recorded in four controls in whom the three tests were projected onto the same retinal areas as in the patients. Evoked responses were more often recorded in the preferred retinal locus of the treated patients with age-related macular degeneration than in the corresponding retinal areas of the controls. The scanning laser ophthalmoscope allowed us to control the site of stimulation in the patients' and controls' retinas. These preliminary results suggest that there may be a functional plasticity of the visual system after therapeutic laser-induced central scotoma.