CBS is more common in those who live alone and have limited social contacts. Other risk factors for CBS include loss of energy, low extroversion, shyness, use of beta-blocker medications, loneliness or bereavement [55]. Typically an episode of CBS is brief, lasting only a few seconds to minutes, and they tend to occur more often in the evening. In one study, about half of the patients reported that their visual hallucinations typically lasted between 1 and 60 min [44]. About a quarter to a third of patients with CBS experience visual hallucinations daily, whereas about half experience them weekly or monthly. The frequency and durations of the visual hallucinations can vary within and between individuals. They tend to last longer when the individual is drowsy or tired, indicating a relationship with the patient’s state of arousal [54]. As with photopsias, some potential triggers for CBS include stress and fatigue. CBS is more likely to occur in low levels of illumination, whereas photopsias are associated with either absence of light or bright light, but more often with bright light [37].

Patients report that they have little control over the appearance or duration of the images. Some patients are able to stop their hallucinations through rapid closing and opening the eyes, blinking, sustained eye closure, turning on a light, looking at something else for distraction, walking away, or hitting or shouting at the hallucination when alone [12]. Potential treatments may include optical devices, such as prisms or telescopes, tinted lenses, use of night lights in the bedroom or increasing social contacts [37]. There are some case reports indicating that some of the atypical antipsychotic or antiepileptic medications can alleviate symptoms; however their effectiveness in clinical trials has not been established [13, 44].

5.5  Filling-In Phenomena (Perceptual Completion)

In order to explain the visual deficit in macular degeneration to people with normal vision, an image is often presented showing a black splotch in the middle of the picture. While this conveys the fact that it is the central vision that is involved, most patients do not see a black splotch. Instead, they report that things are blurry. Patients seem to be able to distinguish this type of blurriness from the difficulty of seeing small print, for example. The blurriness is a result of the patient’s brain and visual system trying to “fill-in” what is not seen [41]. The area corresponding to the scotoma cannot look clear, because in truth the image is not being seen. But the image is completed, and the patients are often not aware that the reason they cannot recognize a face is that parts are really missing.

The filling-in phenomenon or perceptual completion has been associated with the difficulty appreciating a scotoma on Amsler grid testing. The Amsler grid is a square of graph paper, subtending 20° horizontally and vertically at the defined viewing distance. There is a large dot in the middle of the grid. The way in which this test is generally used is to try to have the patient center the eye on the grid (for example, by seeing the four corners of the grid), and then report if the central dot can be seen. (Alternatively, the patient is told to look directly at the dot). The task

is to determine if any of the lines of the grid are distorted, wavy, or missing. The Amsler grid often is used to try to help patients with AMD detect the early development of wet AMD by detecting a distortion in the grid. However, patients who have definite blind spots on visual field testing often cannot detect any part of the grid to be missing or distorted. One study found that 40% of patients with absolute scotomas in their central field, from the heavy laser treatment used for macular degeneration in the past, could not detect a defect on Amsler grid testing [14]. This was further examined by placing the grid directly over the scotoma in a scanning laser ophthalmoscope, in which the examiner could see that it was directly over the blind area. The patients still could not detect the defect on the Amsler grid testing [46].

There are ways to make the patient aware of where filling-in is taking place. In a technique using face fields [49], the patient is instructed to cover one eye. The patient is told to look at the nose of the examiner, so that the nose is seen as clearly as possible. While the patient is looking at the nose, he/she is asked if there is any part of the face that is blurry, distorted, or missing. The face is a very salient stimulus, and patients are often able to say that an eye is missing, or a piece of the cheek is blurred, etc. This is very helpful for defining the location of the preferred retinal locus of fixation (see section 5.7), to allow for more effective low vision training.

5.6  Remapping of Primary Visual Cortex in Patients with Central Scotomas from Macular Disease

Much of the primary visual cortex is devoted to representing the macula [28, 48]. When there are central scotomas, so that much of the macula is blind, what happens to the corresponding areas of primary visual cortex? [25]. Do they remain silent, are they somehow recruited by surrounding retinal areas, or are they stimulated by other cerebral areas? Certainly, cortical areas corresponding to other sensory modalities do not remain silent. For example, there is the phantom limb phenomenon following amputation [17]. For vision, there is the additional question as to whether the potential remapping of the visual cortex could contribute to the use of an eccentric retinal locus of fixation as a “pseudofovea” [59].

Functional MRI (fMRI) can be used to perform retinotopic mapping of the visual cortex [12]. One can have the patient observe a given pattern on a monitor and measure which cortical areas are stimulated by the differential amount of oxygen consumption in each area. Interest has focused on whether there remain silent areas in the primary visual cortex, corresponding to the macular scotomas, or whether there is remapping and therefore activity in these areas that previously subserved the now scotomatous macular region. Work in this area has been ongoing for only the past 5 years. Current information suggests that cortical remapping occurs only when the fovea itself is scotomatous. When the fovea is seeing, the visual cortex corresponding to a scotoma in the macular region near it does not appear to have remapping [3, 4, 36, 51]. One paper reported more stimulation of the so-called lesion projection zone when the eccentric preferred retinal locus of

fixation was stimulated [47]. The stimulation of the lesion projection zone may be task-related [36], and may be from higher cortical levels. When patients with central scotomas were shown scrambled patterns, there were silent areas in the primary visual cortex. When the same patients were shown faces, the formerly silent areas were stimulated, and the face-specific extrastriate cortex was stimulated as well (Rosenau BJ, Greenberg AS, Sunness JS, Yantis S. Cortical Lesion Projection Zone activity in Retinal Disease Patients is Caused by Object-Specific Feedback, not Plasticity, presented at the 2008 VSS Meeting). The hypothesis is that there may be top-down stimulation of primary visual cortex. This may relate to the filling-in phenomenon described above.

5.7  The Preferred Retinal Locus for Fixation

When the fovea is no longer functional, the patient must use an eccentric retinal area to fixate and view the object of interest. Patients vary widely in their ability to create a “pseudofovea”, that is an eccentric preferred retinal locus (PRL) to which the oculomotor system can direct the object of interest [59]. It is not understood why some patients are able to adopt an eccentric PRL effectively and read a chart by looking up or to a side, while other patients with similar scotomas must use repeated scanning movements, report letters coming in and out of view, and have much greater difficulty in reading.

There is evidence that adoption of an eccentric PRL can improve visual acuity. In a prospective study of patients with bilateral advanced dry AMD (geographic atrophy) followed for 3 years, 17% improved their visual acuity by at least 0.2 logMAR (i.e., seeing letters 2/3 the size or smaller) over the course of the follow-up [50]. This improvement occurred only in the worse-seeing eye at baseline, and occurred despite continual enlargement of the central scotoma over the 3-year period. Scanning laser ophthalmoscope analysis showed that at baseline, these worse-seeing eyes could not use peripheral retina effectively; the fixation cross was placed within the scotomatous area where it was not seen, and it could not be stably placed on seeing eccentric retina. At 3 years, these worse-seeing eyes had acquired the ability to use an eccentric retinal locus for fixation, with consequent improvement in visual function. The same improvement did not happen in the better-seeing eyes, presumably because these eyes already were using eccentric retinal fixation loci at baseline. With both eyes open, the better-seeing eye’s fixation pattern likely dominated the two eyes, perhaps interfering with the development of a monocular PRL in the worse-seeing eye. By 3 years, with worsening of the better eye as well, more attention was now directed to the worse-seeing eye, with improved use of peripheral seeing retina and consequent improvement in visual function.

This spontaneous improvement in visual acuity in the worse-seeing eye has important implications for future clinical trials for retinal prostheses. In all likelihood, the eye to be treated initially for each patient will be the one with worse