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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. Electronic supplementary material The online version of this article (10.1007/s00429-018-1700-7) contains supplementary material, which is available to authorized users.

Chordoid glioma of the third ventricle (CGTV) is a rare, slow-growing, World Health Organization Grade II glial tumor, with stereotyped localization in the anterior third ventricle. Despite being considered a noninvasive tumor, CGTV is usually associated with a poor clinical outcome due to its close proximity to important cerebral structures, such as the hypothalamus and visual pathways. Our patient with CGTV experienced visual involvement, but after subtotal surgical resection showed no evidence of progression at 5-year follow-up.

Emerging evidence suggests that white matter plasticity in the adult brain is preserved after sensory and behavioral modifications. However, little is known about the progression of structural changes during the process of decline in visual input. Here we studied two groups of patients suffering from advanced retinitis pigmentosa with specific deterioration of the visual field: patients who had lost their peripheral visual field, retaining only central (“tunnel”) vision, and blind patients with complete visual field loss. Testing of these homogeneous groups made it possible to assess the extent to which the white matter is affected by loss of partial visual input and whether partially preserved visual input suffices to sustain stability in tracts beyond the primary visual system. Our results showed gradual changes in diffusivity that are indicative of degenerative processes in the primary visual pathway comprising the optic tract and the optic radiation. Interestingly, changes were also found in tracts of the ventral stream and the corticospinal fasciculus, depicting a gradual reorganisation of these tracts consequentially to the gradual loss of visual field coverage (from intact perception to partial vision to complete blindness). This reorganisation may point to microstructural plasticity underlying adaptive behavior and cross-modal integration after partial visual deprivation.

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Background: Understanding limitations on text reading with eccentric fixation is of major concern in low vision research. Our objective was to determine, in patients with a central scotoma, whether threshold character size is similar for different word lengths and paragraphed texts. Methods: In 19 patients, we retrospectively analyzed the relationship between minimum readable character size for isolated words and text. Isolated letters, two, five, and ten-letter words and a paragraphed text were presented randomly through a scanning laser ophthalmoscope in eight different character sizes. Results: Threshold character size varied according to the text stimulus (p0.99), as were those for five-letter words, ten-letter words, and paragraphed text (p>0.99). Threshold character size for single letters and two-letter words was significantly lower than that measured with other text stimuli. Discussion: Reading performance is influenced by a variety of factors such as crowding, contextual effects, visual span, degree of oculomotor adaptation needed, and frequency of a defined word. Globally, when reading with a central scotoma, it appears that within word characteristics have more impact than inter-word parameters on threshold character size

Behavioral alterations emerging after central or peripheral vision loss suggest that cerebral reorganization occurs for both the afferented and deafferented early visual cortex (EVC). We explored the functional reorganization of the central and peripheral EVC following visual field defects specifically affecting central or peripheral vision. Compared to normally sighted, afferented central and peripheral EVC enhance their functional connectivity with areas involved in visual processing, whereas deafferented central and peripheral EVC increase their functional connectivity with more remote regions. The connectivity pattern of afferented EVC suggests adaptive changes that might enhance the visual processing capacity whereas the connectivity pattern of deafferented EVC may reflect the involvement of these regions in high-order mechanisms. Characterizing and understanding the plastic changes induced by these visual defects is essential for any attempt to develop efficient rehabilitation strategies.

International audience; In the congenitally blind, language processing involves visual areas. In the case of normal visual development however, it remains unclear whether later visual loss induces interactions between the language and visual areas. This study compared the resting-state functional connectivity (FC) of retinotopic and language areas in two unique groups of late visually deprived subjects: (1) blind individuals suffering from retinitis pigmentosa (RP), (2) RP subjects without a visual periphery but with preserved central “tunnel vision”, both of whom were contrasted with sighted controls. The results showed increased FC between Broca's area and the visually deprived areas in the peripheral V1 for individuals with tunnel vision, and both the peripheral and central V1 for blind individuals. These findings suggest that FC can develop in the adult brain between the visual and language systems in the completely and partially blind. These changes start in the deprived areas and increase in size (involving both foveal and peripheral V1) and strength (from negative to positive FC) as the disease and sensory deprivation progress. These observations support the claim that functional connectivity between remote systems that perform completely different tasks can change in the adult brain in cases of total and even partial visual deprivation.

Purpose The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Design Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients’ native residual vision compared with their vision with the Argus II. Participants Thirty participants in 10 centers in the United States and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Results Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. Conclusions The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. © 2016 American Academy of Ophthalmology

BACKGROUND Cortical remapping after peripheral or central visual deafferentation alters visual perception, but it is unclear whether such a phenomenon impinges on areas remote from a scotoma. To investigate this question, we studied variations of perceptual spatial distortion in the visual field of patients with homonymous paracentral scotoma. METHODS Two patients with right inferior homonymous paracentral scotoma were asked to describe their perception of a series of figures showing two isometric vertical lines symmetrically located on either side of a fixation point. In each figure, the fixation point varied by steps of 2 degrees along a hypothetical vertical line equidistant between the test lines. The lines subtended 20 degrees of visual angle, and the right line passed through the scotoma in both cases. Time for spatial distortion to manifest was recorded. RESULTS Both subjects reported that the right line was perceived as shorter than the left one. The line shortening varied in magnitude with the distance of the fixation point from the end of the line and was more pronounced when the distance increased. Moreover, perceptual line shortening appeared 5-10 seconds after steady fixation, but values of shortening varied during the following 10 seconds. In addition, the right line appeared uninterrupted or slightly blurred in the scotoma region. CONCLUSIONS These observations reflect long-range cortical reorganization after brain damage. Larger receptive fields in the periphery of the visual map could explain why perceptual shortening is more pronounced with increased eccentricity.

Age-related macular degeneration is a retinal disease causing the progressive loss of macular vision, typically in people over 60 years of age. It will become a major public health problem in the next years as the population of aged people is expected to increase. In the advanced stage of the disease, development of the central retinal lesion provokes a central scotoma in the visual fi eld. Consequently, at this stage, patients only rely on the use of peripheral vision to achieve visual tasks. The exclusive use of the peripheral retina itself modifi es visual perception by reducing visual acuity and con- trast sensitivity, and by increasing crowding effects, i.e. contour interaction. Visual perception is further modifi ed by mechanisms of cortical plasticity taking place following the development of the retinal lesion. These mechanisms induce a variety of perceptual changes including fi lling-in, altered perception of space and Charles Bonnet syndrome. While some modifi cations of visual perception, such as reduction of visual acuity and contrast sensitivity are well known, occurrence of other phenomena like crowding effect and Charles Bonnet syndrome is generally underestimated. The aim of this review is to discuss the major factors modifying visual perception in patients with advanced age-related macular degeneration and to relate these phenomena to patients' visual diffi culties in everyday life.

The exquisite sensitivity of the human visual system to form-from-motion (FfM) cues is well documented. However, identifying the neural correlates of this sensitivity has proven difficult, particularly determining the respective contributions of different motion areas in extrastriate visual cortex. Here we measured visual FfM perception and more elementary visual motion (VM) perception in a group of 32 patients suffering from acute posterior brain damage, and performed MRI-based lesion analysis. Our results suggest that severe FfM perception deficits without an associated deficit of VM perception are due to damage to ventral occipito-temporal cortex (VOT), whereas associated deficits of FfM and VM perception are due to damage either in proximity to area MT+/V5 or an area including lateral occipital complex (LOC) and VOT. These data suggest the existence of at least three functionally and anatomically distinct regions in human visual cortex that process FfM signals.

© 2015 American Academy of Ophthalmology. Purpose Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. Design The study is a multicenter, single-arm, prospective clinical trial. Participants There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). Methods The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Results A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. Conclusions The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Background: In age related macular degeneration and inherited dystrophies, preservation of retinal ganglion cells has been demonstrated. This finding has led to the development of various models of subretinal or epiretinal implant in order to restore vision. This study addresses the development of a polyimide subretinal electrode platform in the dystrophic P23H rat in vivo. Methods: A technique was developed for implanting a subretinal electrode into the subretinal space and stabilising the distal extremity of the cabling on the rat cranium in order to allow future electrical stimulations of the retina. Results: In vivo imaging of the retina with the scanning laser ophthalmoscope demonstrated reabsorption of the surgically induced retinal detachment and the absence of major tissue reactions. These in vivo observations were confirmed by retinal histology. The extraocular fixation system on the rat cranium was effective in stabilising the distal connector for in vivo stimulation. Conclusion: This study demonstrates that a retinal implant can be introduced into the subretinal space of a dystrophic rat with a stable external connection for repeatable electrical measurements and stimulation. This in vivo model should therefore allow us to evaluate the safety and efficacy of electrical stimulations on dystrophic retina.

Motion blindness (MB) is defined as the selective disturbance of visual motion perception despite intact perception of other features of the visual scene. MB is characterized by a pandirectional deficit of motion direction discrimination and is assumed to result from damage to the visual motion pathway, especially area MT/V5. However, the most characteristic feature of primate MT/V5 neurons is not their motion selectivity but their preference for one direction of motion (direction selectivity), which changes incrementally at neighbouring columns. In addition to this microscopic directional organization, studies in nonhuman and human primates suggest that single directions of motion are also coded at a more macroscopic level. We thus hypothesized that if MB in humans results from damage to direction-selective neurons in the visual motion pathway, posterior brain damage might cause MB which is direction selective, not pandirectional. The present study investigated motion direction discrimination in patients with posterior unilateral brain damage and determined separate psychophysical thresholds for the four cardinal directions. In addition, we analysed whether the direction of erroneous motion perception (i.e. the perception of right motion for upward motion) was random or showed a directional bias. We report three principal findings. First, motion direction discrimination was severely impaired in one or two directions while it was normal in the other directions. This constituted direction-selective MB. Second, MB was characterized not only by a quantitative direction-selective increase in psychophysical thresholds but also by a qualitative impairment of perceiving motion direction systematically in wrong directions. Both findings suggest that the cortical modules specialized for the perception of a single direction of motion might be larger than previously thought. Third, lesion analysis showed that unilateral damage, not only the human homologue of MT/V5 but also to parieto-occipital cortex, leads to MB.

Simulations of artificial vision were performed to assess "minimum requirements for useful artificial vision". Retinal prostheses will be implanted at a fixed (and probably eccentric) location of the retina. To mimic this condition on normal observers, we projected stimuli of various sizes and content on a defined stabilised area of the visual field. In experiment 1, we asked subjects to read isolated 4-letter words presented at various degrees of pixelisation and at various eccentricities. Reading performance dropped abruptly when the number of pixels was reduced below a certain threshold. For central reading, a viewing area containing about 300 pixels was necessary for close to perfect reading (>90% correctly read words). At eccentricities beyond 10 degrees, close to perfect reading was never achieved even if more than 300 pixels were used. A control experiment using isolated letter recognition in the same conditions suggested that lower reading performance at high eccentricity was in part due to the "crowding effect". In experiment 2, we investigated whether the task of eccentric reading under such specific conditions could be improved by training. Two subjects, naive to this task, were trained to read pixelised 4-letter words presented at 15 degrees eccentricity. Reading performance of both subjects increased impressively throughout the experiment. Low initial reading scores (range 6%-23% correct) improved impressively (range 64%-85% correct) after about one month of training (about 1 h/day). Control tests demonstrated that the learning process consisted essentially in an adaptation to use an eccentric area of the retina for reading. These results indicate that functional retinal implants consisting of more than 300 stimulation contacts will be needed. They might successfully restore some reading abilities in blind patients, even if they have to be placed outside the foveal area. Reaching optimal performance may, however, require a significant adaptation process.

Motion blindness (MB) or akinetopsia is the selective disturbance of visual motion perception while other features of the visual scene such as colour and shape are normally perceived. Chronic and transient forms of MB are characterized by a global deficit of direction discrimination (pandirectional), which is generally assumed to result from damage to, or interference with, the motion complex MT+/V5. However, the most characteristic feature of primate MT-neurons is not their motion specificity, but their preference for one direction of motion (direction specificity). Here, we report that focal electrical stimulation in the human posterior temporal lobe selectively impaired the perception of motion in one direction while the perception of motion in other directions was completely normal (unidirectional MB). In addition, the direction of MB was found to depend on the brain area stimulated. It is argued that direction specificity for visual motion is not only represented at the single neuron level, but also in much larger cortical units.

Purpose of review Synesthesia is an extraordinary perceptual phenomenon, in which individuals experience unusual percepts elicited by the activation of an unrelated sensory modality or by a cognitive process. Emotional reactions are commonly associated. The condition prompted philosophical debates on the nature of perception and impacted the course of art history. It recently generated a considerable interest among neuroscientists, but its clinical significance apparently remains underevaluated. This review focuses on the recent studies regarding variants of color synesthesia, the commonest form of the condition. Recent findings Synesthesia is commonly classified as developmental and acquired. Developmental forms predispose to changes in primary sensory processing and cognitive functions, usually with better performances in certain aspects and worse in others, and to heightened creativity. Acquired forms of synesthesia commonly arise from drug ingestion or neurological disorders, including thalamic lesions and sensory deprivation (e.g., blindness). Cerebral exploration using structural and functional imaging has demonstrated distinct patterns in cortical activation and brain connectivity for controls and synesthetes. Artworks of affected painters are most illustrative of the nature of synesthetic experiences. Summary Results of the recent investigations on synesthesia offered a remarkable insight into the mechanisms of perception, emotion and consciousness, and deserve attention both from neuroscientists and from clinicians.

Purpose With a retinal prosthesis connected to a head-mounted camera (camera-connected prosthesis [CC-P]), subjects explore the visual environment through head-scanning movements. As eye and camera misalignment might alter the spatial localization of images generated by the device, we investigated if such misalignment occurs in blind subjects wearing a CC-P and whether it impacts spatial localization, even years after the implantation. Methods We studied three subjects blinded by retinitis pigmentosa, fitted with a CC-P (Argus II) 4 years earlier. Eye/head movements were video recorded as subjects tried to localize a visual target. Pointing coordinates were collected as subjects were requested to orient their gaze toward predetermined directions, and to point their finger to the corresponding perceived spot locations on a touch screen. Finally, subjects were asked to give a history of their everyday behavior while performing visually controlled grasping tasks. Results Misaligned head and gaze directions occurred in all subjects during free visual search. Pointing coordinates were collected in two subjects and showed that median pointing directions shifted toward gaze direction. Reportedly all subjects were unable to accurately determine their eye position, and they developed adapted strategies to perform visually directed movements. Conclusions Eye position affected perceptual localization of images generated by the Argus II prosthesis, and consequently visuomotor coordination, even 4 years following implantation. Affected individuals developed strategies for visually guided movements to attenuate the impact of eye and head misalignment. Our observations provide indications for rehabilitation procedures and for the design of upcoming retinal prostheses. (ClinicalTrials.gov number, NCT00407602.).

To investigate the use of several preferred retinal loci (PRL) when attempting to read, two patients with bilateral central scotomas were asked to decipher single words, successively projected onto the retina using a scanning laser ophthalmoscope (SLO). Video-recordings of the fundus image, on which the projected targets were superimposed, were analyzed frame by frame. One patient used two PRL in association and the other used three, each PRL having a specific function. Single word reading made it easier than with full texts to correlate the images parts scrutinized and the retinal areas involved. Then, as patients were unable to describe their reading behavior, the examiner monitored refixation movements using the SLO and asked questions to help them to become aware of their reading behavior. Eventually, they could localize their PRL, describe their specific functions, and switch at will between them.

In 106 children aged 5–8 years, we determined how much training was needed to stabilize the response strategy prior to actual visual field assessment and we evaluated the reliability and acceptable duration of automated static perimetry (Octopus 2000R). A specially designed familiarization procedure was used to train the children to: (1) gaze at the center of the visual field while paying attention to light stimuli projected onto the periphery and (2) press the buzzer only when light stimuli were perceived. The subsequent examination phase consisted of 15 successive identical blocks of 27 trials (12 stimulus trials, 12 false-positive catch-trials, and three false-negative catch-trials), and was stopped before the end if signs of fatigue appeared. Age had a marked influence both on endurance (the number of blocks performed increased significantly) and on response reliability (false-positive responses decreased between 5- and 6-year-olds). The increase in false-negative responses toward the end indicates that examination is no longer reliable, and should be stopped. We concluded that most children as young as five can undergo examination by automated static perimetry. Changes regarding learning, stimulus intensity and testing procedure are suggested in order to adapt the examination to age, level of vigilance and health condition of the children.

AIMS--To investigate how young children develop the ability to undergo a visual field evaluation using regular automated perimetry. METHODS--The study included 42 normal girls aged 5, 6, 7, and 8 years. Twelve locations in the 15 degrees eccentricity were tested in one eye, using an Octopus 2000R perimeter with a two level strategy. False positive and false negative catch trials were presented. The examination was performed three times in succession. Before the examination procedure, a specially designed programme was conducted for progressive familiarisation. RESULTS--During the familiarisation procedure, it was found that all of the 5-year-old children, seven of the 6-year-old children, and three of the 7-year-old children were unable to perform immediately, and correctly, the instructions given during the familiarisation phase; these children took from 30 seconds to 3 minutes to comply with the examiner's requests. With the exception of one 5-year-old child, all tested subjects completed the planned procedure. The mean proportion of false negative answers in catch trials was 1.6%. The mean proportion of false positive answers was 12.2%. The quadratic dependency on age suggested by the averages was not significant (F(3,116) = 0.88; p = 0.45). Detection stimulus improved with age, as shown by the fact that probability of perceiving dim stimulus increases significantly (F(3,116) = 12.68; p < 0.0001). CONCLUSION--Children did remarkably well regarding both the duration of the examination and the reliability of the answers. A preliminary familiarisation phase with a specially designed adaptation programme was found to be mandatory with children aged 7 or under. To our knowledge, this is the first time that such an investigation has been performed.

Purpose This study evaluated the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in blind subjects with severe outer retinal degeneration. Design Single-arm, prospective, multicenter clinical trial. Participants Thirty subjects were enrolled in the United States and Europe between June 6, 2007, and August 11, 2009. All subjects were followed up for a minimum of 6 months and up to 2.7 years. Methods The electronic stimulator and antenna of the implant were sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed, and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array then was tacked to the epiretinal surface. Main Outcome Measures The primary safety end points for the trial were the number, severity, and relation of adverse events. Principal performance end points were assessments of visual function as well as performance on orientation and mobility tasks. Results Subjects performed statistically better with the system on versus off in the following tasks: object localization (96% of subjects), motion discrimination (57%), and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects' mean performance on orientation and mobility tasks was significantly better when the system was on versus off. Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was treated successfully in all subjects except in one, who required explantation of the device without further complications. Conclusions The long-term safety results of Second Sight's retinal prosthesis system are acceptable, and most subjects with profound visual loss perform better on visual tasks with system than without it. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Background Subjects with a ring scotoma can use two retinal loci, a foveal and a peripheral, for reading. Our aim was to investigate the relative use of both retinal loci as a function of the spared foveal area size and the spatial resolution at both retinal loci. Findings Two patients with Stargardt's disease and ring scotomas read through a scanning laser ophthalmoscope a series of letters and words at various character sizes. The number of fixations made using each retinal locus was quantified. The relative use of each retinal locus depended on character size of the stimulus. Both patients used exclusively the eccentric retinal locus to read words of large character sizes. At small character sizes, the central retinal locus was predominantly used. For reading letters or words, once foveal fixation was used, patients did not shift back to the eccentric retinal locus. When spatial resolution allowed deciphering at both the eccentric and the central areas, patients consistently fixated with the eccentric retinal locus. Conclusions Spatial resolution at the eccentric locus appears as a determinant factor to select the retinal area for reading. Reading strategies in patients with Stargardt's disease and a ring scotoma demonstrate a pattern of coordination of both eccentric and central retinal loci, reflecting a high degree of adaptation.

BACKGROUND: The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. METHODS: A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. RESULTS: We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). CONCLUSION: The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field.

BACKGROUND: In vivo confocal microscopy (IVCM) is a newly developed application to assess corneal nerve morphology. The purpose of the study is to evaluate the role of IVCM in the assessment of various types of polyneuropathy, and to define alterations of corneal nerves in such conditions. PATIENTS AND METHODS: Eighteen patients with various types of polyneuropathy were characterized by clinical neurological and ophthalmic examinations, as well as by electroneuromyography (ENMG). Full thickness IVCM of corneal nerves was carried out on all patients and 15 age-matched eyes using Heidelberg Retina Tomograph II (HRT II). The subbasal nerve plexus were statistically analysed regarding long nerve fiber density, nerve branch density, nerve thickness, nerve bead number and nerve tortuosity. RESULTS: In subbasal nerve plexus, the following three parameters were significantly reduced in patients with polyneuropathy compared to controls: long nerve fibre density (p < 0.01), nerve branch density (p < 0.001), and nerve bead number (p = 0.001). In addition, the average grade of nerve tortuosity was 2.87 +/- 0.97 in the polyneuropathic group and 1.17 +/- 0.68 in the control group (p < 0.0001). CONCLUSIONS: IVCM allows a non-invasive, in vivo study of corneal nerves with high resolution. It therefore appears invaluable in clinical investigations. IVCM appears to be valuable in a large variety of polyneuropathic conditions.

After a low brainstem stroke, a 73-year-old man experienced episodes of 90 degrees tilting of the visual environment in the sagittal plane evoked or terminated by voluntarily changing his head position. The episodes ceased 10 days after the stroke. This provocation by head position supports the idea that pathologic visual-vestibular interaction is at the basis of the room tilt illusion.

Retinal prostheses attempt to restore some amount of vision to totally blind patients. Vision evoked this way will be however severely constrained because of several factors (e.g., size of the implanted device, number of stimulating contacts, etc.). We used simulations of artificial vision to study how such restrictions of the amount of visual information provided would affect performance on simple pointing and manipulation tasks. Five normal subjects participated in the study. Two tasks were used: pointing on random targets (LEDs task) and arranging wooden chips according to a given model (CHIPs task). Both tasks had to be completed while the amount of visual information was limited by reducing the resolution (number of pixels) and modifying the size of the effective field of view. All images were projected on a 10 degrees x 7 degrees viewing area, stabilised at a given position on the retina. In central vision, the time required to accomplish the tasks remained systematically slower than with normal vision. Accuracy was close to normal at high image resolutions and decreased at 500 pixels or below, depending on the field of view used. Subjects adapted quite rapidly (in less than 15 sessions) to performing both tasks in eccentric vision (15 degrees in the lower visual field), achieving after adaptation performances close to those observed in central vision. These results demonstrate that, if vision is restricted to a small visual area stabilised on the retina (as would be the case in a retinal prosthesis), the perception of several hundreds of retinotopically arranged phosphenes is still needed to restore accurate but slow performance on pointing and manipulation tasks. Considering that present prototypes afford less than 100 stimulation contacts and that our simulations represent the most favourable visual input conditions that the user might experience, further development is required to achieve optimal rehabilitation prospects.

Summary: Purpose: The risk factors for visual field loss attributable to vigabatrin (VAVFL) are equivocal. This multinational, prospective, observational study aimed to clarify the principal/major factors for VAVFL. Methods: Interim analysis of three groups with refractory partial epilepsy, stratified by age (8‐12 years; >12 years) and exposure to vigabatrin (VGB). Group I comprised participants treated with VGB for ≥6 months, Group II participants previously treated with VGB for ≥6 months who had discontinued the drug for ≥6 months and Group III those never treated with VGB. Perimetry was undertaken at least every six months, for up to 36 months; results were evaluated masked to drug exposure. Results: Based upon 563 participants in the locked data set, 432 yielded one or more Conclusive visual field examinations. For Group I, the frequency of VAVFL at the last Conclusive examination was 10/32 (31.2%) for those aged 8‐12 years and 52/125 (41.6%) for those aged >12 years. For Group II, the proportions were 4/39 (10.3%) and 31/129 (24.0%). No cases resembling VAVFL manifested in Group III. VAVFL was associated with duration of VGB therapy (Odds ratio [OR] 14.2; 95% CI 5.0 to 40.5); mean dose of VGB (OR 8.5; 95% CI 2.2 to 33.2); and male gender (OR 2.1; 95% CI 1.2 to 3.7). VAVFL was more common with static than kinetic perimetry (OR 2.3, 95% CI 1.3 to 4.2). Conclusions: The therapeutic benefit of VGB is counteracted by the progressive accrual of the risk of VAVFL with continued exposure and with increase in mean dose.

Background Reading with a central scotoma involves the use of preferred retinal loci (PRLs) that enable both letter resolution and global viewing of word. Spontaneously developed PRLs however often privilege spatial resolution and, as a result, visual span is commonly limited by the position of the scotoma. In this study we designed and performed the pilot trial of a training procedure aimed at modifying oculomotor behavior in subjects with central field loss. We use an additional fixation point which, when combined with the initial PRL, allows the fulfillment of both letter resolution and global viewing of words. Methods The training procedure comprises ten training sessions conducted with the scanning laser ophthalmoscope (SLO). Subjects have to read single letters and isolated words varying in length, by combining the use of their initial PRL with the one of an examiner's selected trained retinal locus (TRL). We enrolled five subjects to test for the feasibility of the training technique. They showed stable maculopathy and persisting major reading difficulties despite previous orthoptic rehabilitation. We evaluated ETDRS visual acuity, threshold character size for single letters and isolated words, accuracy for paragraphed text reading and reading strategies before, immediately after SLO training, and three months later. Results Training the use of multiple PRLs in patients with central field loss is feasible and contributes to adapt oculomotor strategies during reading related tasks. Immediately after SLO training subjects used in combination with their initial PRL the examiner's selected TRL and other newly self-selected PRLs. Training gains were also reflected in ETDRS acuity, threshold character size for words of different lengths and in paragraphed text reading. Interestingly, subjects benefited variously from the training procedure and gains were retained differently as a function of word length. Conclusion We designed a new procedure for training patients with central field loss using scanning laser ophthalmoscopy. Our initial results on the acquisition of newly self-selected PRLs and the development of new oculomotor behaviors suggest that the procedure aiming primarily at developing an examiner's selected TRL might have initiated a more global functional adaptation process.

Among the spectrum of infectious keratites, acanthamoeba keratitis (AK) represents one of the most difficult entities to diagnose and to treat properly, thus threatening the visual function. It affects immunocompetent patients and the main risk factors for the development of AK are the use of contact lenses, the exposure to contaminated water or contact lens solution, and corneal trauma.1 Clinically, this infection may appear as corneal stromal infiltrates, recurrent epithelial erosions, disciform keratitis, and keratoneuritis. An anterior uveitis and/or a hypopyon may be present too. The diagnosis is usually made by scraping and culturing the corneal tissue and by performing a corneal biopsy if the epithelium is intact. We report the case of a patient with an AK diagnosed by culturing the hypopyon. We would like to emphasise the value of this procedure in making the diagnosis in patient suffering from AK. An 81 …

INTRODUCTION: A prominent neurophysiological model of phobia generation holds that specific phobia might result from the uncoupling of unaware subcortical fear responses from aware cortical fear responses. Former responses are thought to be automatic and fast, providing approximate information about the external stimulus, whereas the latter responses are more controlled and allow comparison with previous experience. Since only the cortical pathway carries information available to awareness, this model also accounts for the striking irrationality of specific phobia in humans. METHODS: Here, we report neuropsychological and neuro-ophthalmological findings in a 41-year-old patient who developed severe dog phobia following bilateral parietal lobe damage. RESULTS: The examinations showed a severe deficit in visual motion perception (visual motion blindness or akinetopsia) as well as spatial vision. Importantly, the patient was largely unaware of his visual deficits. CONCLUSION: Based on the present observation it is argued that irrational fear, as found in specific phobia, might not only result from a general uncoupling of aware cortical from unaware subcortical fear responses, but also from a functionally similar dissociation at the cortical level.

Determining causes of poor reading ability is an important step in trying to ameliorate reading performance in low-vision patients. One important parameter is word acuity. The principal aim of the current study is to develop a method to reliably measure acuities for isolated lowercase letters and words of differing length that can be used to test low-vision patients. Using isolated stimuli means that testing is relatively free of potential crowding and/or distracting attentional effects from surrounding words, it is unambiguous which stimulus subjects are trying to read and response times can be recorded for each stimulus. Across a series of experiments, subjects with normal vision were asked to read isolated lowercase single letters and lowercase words of 4, 7 and 10 letters, in separate tests. Acuities for uppercase Sloan letters were also measured to provide a reference, as they are commonly used to measure visual acuity. Each test was based upon the design principles and scoring procedures used in the Bailey-Lovie and ETDRS charts. Acuities for uppercase Sloan letters were found to be equivalent whether measured using ETDRS charts or the computer-based method. Measurement of acuities for lowercase single letters and lowercase words of 4, 7 and 10 letters had a reliability that was no worse than acuities for uppercase Sloan letters. Lowercase word acuities were essentially independent of word length. Acuities for single lowercase letters and lowercase words were slightly better than uppercase Sloan letters acuity. Optimal processing of lowercase single letters and 4-, 7- and 10-letter words occurred at character sizes that were at least 0.2-0.40 log MAR above acuity threshold, i.e. between 1.5 and 3 times threshold acuity for that particular stimulus. In general, critical character sizes appear similar across word lengths as progressive increases or decreases in these values were not observed as a function of the number of letters in the stimulus. We conclude that a computer-based method of stimulus presentation can be used to obtain highly repeatable measures of acuity for lowercase single letters and lowercase words in normal vision.

Adaptation to eccentric viewing in subjects with a central scotoma remains poorly understood. The purpose of this study was to analyze the adaptation stages of oculomotor control to forced eccentric reading in normal subjects.Three normal adults (25.7 +/- 3.8 years of age) were trained to read full-page texts using a restricted 10 degrees x 7 degrees viewing window stabilized at 15 degrees eccentricity (lower visual field). Gaze position was recorded throughout the training period (1 hour per day for approximately 6 weeks).In the first sessions, eye movements appeared inappropriate for reading, mainly consisting of reflexive vertical (foveating) saccades. In early adaptation phases, both vertical saccade count and amplitude dramatically decreased. Horizontal saccade frequency increased in the first experimental sessions, then slowly decreased after 7 to 15 sessions. Amplitude of horizontal saccades increased with training. Gradually, accurate line jumps appeared, the proportion of progressive saccades increased, and the proportion of regressive saccades decreased. At the end of the learning process, eye movements mainly consisted of horizontal progressions, line jumps, and a few horizontal regressions.Two main adaptation phases were distinguished: a "faster" vertical process aimed at suppressing reflexive foveation and a "slower" restructuring of the horizontal eye movement pattern. The vertical phase consisted of a rapid reduction in the number of vertical saccades and a rapid but more progressive adjustment of remaining vertical saccades. The horizontal phase involved the amplitude adjustment of horizontal saccades (mainly progressions) to the text presented and the reduction of regressions required.

Serpiginous choroidopathy (SC) is a rare disease inducing a permanent loss of vision, caused by a progressive destruction of the retinal pigment epithelium and choriocapillaris. Until now, no aetiology or predisposing factors have been reported. SC, usually, affects both eyes and occurs in patients between the fourth and sixth decade, without any sex or race predilection. Clinically, deep cream-coloured lesions develop in the peripapillary region and then along the retinal vessels, centrifugally, inducing an atrophy of the retina. Other lesions may develop, isolated, in the posterior segment. The anterior segment is typically quiet; nevertheless, a mild anterior uveitis and/or vitritis have been observed. The course of the disease results in successive attacks and recurrences inducing permanent retinal atrophic changes and subsequently an irreversible loss of vision. Choroidal neovascularisation may occasionally develop. No specific diagnostic tests are available such that the diagnosis of SC is mostly clinical.1 A 30 year old Indian man presented with a history of painless progressive visual loss affecting the right eye. No other ophthalmological or systemic complaints were present. His medical history was unremarkable. Ophthalmological examination revealed a visual acuity of 20/50 in the right eye and 20/20 in the left eye without a correction in both eyes. Anterior segment examination revealed a mild inflammation with fine keratic precipitates on the inferior …

In preceding studies, simulations of artificial vision were used to determine the basic parameters for visual prostheses to restore useful reading abilities. These simulations were based on a simplified procedure to reduce stimuli information content by preprocessing images with a block-averaging algorithm (square pixelization). In the present study, how such a simplified algorithm affects reading performance was examined.Five to six volunteers with normal vision were asked to read full pages of text with a 10 degrees x 7 degrees viewing window stabilized in central vision. In a first experiment, reading performance with off-line and real-time square pixelizations was compared at different resolutions. In a second experiment, off-line square pixelization was compared with off-line Gaussian pixelization with various degrees of overlap. In a third experiment, real-time square pixelization was compared with real-time Gaussian pixelization.Results from the first experiment showed that real-time square pixelization required approximately 30% less information (pixels) than its off-line counterpart. Results from the second experiment, using off-line processing, revealed a restricted range of Gaussian widths for which performances were equivalent or significantly better than that obtained with square pixelization. The third experiment demonstrated, however, that reading performances were similar in both real-time pixelization conditions.This study reveals that real-time stimulus pixelization favors reading performance. Performance gains were moderate, however, and did not allow for a significant (e.g., twofold) reduction of the minimum resolution (400-500 pixels) needed to achieve useful reading abilities.

BACKGROUND: Postoperative bacterial endophthalmitis is caused by the patient's endogenous flora in most cases (80 %). Pasteurella multocida (PM) is a Gram-negative coccobacillus found in the upper respiratory tract of dogs and cats and is very rarely implicated in postoperative endophthalmitis. HISTORY AND SIGNS: We describe a case of PM endophthalmitis that developed after cataract surgery. THERAPY AND OUTCOME: Cultures of both the conjunctiva and the aqueous humor were positive for PM. Topical, intravitreous and intravenous antibiotics were administered. Despite treatment, the outcome was unfavourable and complicated by a corneal perforation. CONCLUSIONS: The prognosis of postoperative PM endophthalmitis remains poor, despite adequate treatment of the infection. A history of recent pet exposure should alert physicians to this possible aetiological factor.

Background: Oculomotor behaviour was investigated in 14 patients with central scotomas from age related macular degeneration (AMD) or Stargardt’s disease. A scanning laser ophthalmoscope (SLO) was used to project letters and words onto the retina and to assess fixation behaviour. Five patients reported while deciphering letters that they needed to “move their eye” to prevent the image from vanishing. The observation of the SLO fundus images revealed that the gradual disappearance of the stimulus did not result from a transient projection of the word in the lesion. This prompted the authors to investigate, in an experimental setting, whether purposeful changes in fixation position could improve the perception of an eccentrically fixated text stimulus. Methods: Twenty normal subjects were asked to alternate fixation, every three to four seconds, between two vertically aligned dots, spaced 10° apart, and to report any changes in the perception of a laterally located letter, 1.5° in height, 7° apart and equidistant between the two fixation spots. Results: Nineteen subjects reported a transient refreshment of the letter image immediately after the realisation of a saccade. Improved perception lasted approximately a second. With persistent fixation, they noted a rapid fading effect that reduced letter recognition. Conclusion: These observations suggest that ocular instability during eccentric viewing can have a functional advantage, probably related to counteracting Troxler’s phenomenon. In addition to alternating between PRLs, it appears that saccades related to fixation instability might be valuable and improve text perception in individuals with a central scotoma and eccentric fixation. This possibility should be taken into consideration when conducting visual rehabilitation procedures.

Reading of isolated words in conditions mimicking artificial vision has been found to be a difficult but feasible task. In particular at relatively high eccentricities, a significant adaptation process was required to reach optimal performances [Vision Res. 43 (2003) 269]. The present study addressed the task of full-page reading, including page navigation under control of subject's own eye movements. Conditions of artificial vision mimicking a retinal implant were simulated by projecting stimuli with reduced information content (lines of pixelised text) onto a restricted and eccentric area of the retina. Three subjects, naive to the task, were trained for almost two months (about 1 h/day) to read full-page texts. Subjects had to use their own eye movements to displace a 10 degrees x 7 degrees viewing window, stabilised at 15 degrees eccentricity in their lower visual field. Initial reading scores were very low for two subjects (about 13% correctly read words), and astonishingly high for the third subject (86% correctly read words). However, all of them significantly improved their performance with time, reaching close to perfect reading scores (ranging from 86% to 98% correct) at the end of the training process. Reading rates were as low as 1-5 words/min at the beginning of the experiment and increased significantly with time to 14-28 words/min. Qualitative text understanding was also estimated. We observed that reading scores of at least 85% correct were necessary to achieve 'good' text understanding. Gaze position recordings, made during the experimental sessions, demonstrated that the control of eye movements, especially the suppression of reflexive vertical saccades, constituted an important part of the overall adaptive learning process. Taken together, these results suggest that retinal implants might restore full-page text reading abilities to blind patients. About 600 stimulation contacts, distributed on an implant surface of 3 x 2 mm2, appear to be a minimum to allow for useful reading performance. A significant learning process will however be required to reach optimal performance with such devices, especially if they have to be placed outside the foveal area.

Although many individuals with a central scotoma develop eccentric fixation most often beneath or left of the scotoma, little is known about how they come to develop a particular viewing strategy. We investigated this by asking eight subjects with normal vision to read isolated letters, words and text passages while an artificial scotoma covered a central portion of the visual field. We quantified viewing strategy and analysed changes in their viewing behaviour over 8-10 sessions within a two-week period. Subjects read while either a horizontal (n=4) or vertical bar scotoma (n=4), 10 degrees wide, covered the entire horizontal or vertical meridian of the stimulus field. For the horizontal scotoma group: (1) there was an increasing preference to use the inferior visual field for isolated letters/words and text passages, which was essentially complete within the test period; (2) the superior visual field was preferred when reading letters/words initially presented in upper visual space and the inferior visual field when reading letters/words initially presented in lower visual space; (3) in general, variation in viewing strategy according to stimulus position diminished over the sessions for all stimuli. For the vertical scotoma group: (1) two subjects used the left and right visual fields in approximately equal proportion to view isolated letters/words, one subject showed a weak preference to use the left visual field and one subject developed a strong preference for using the right visual field; (2) the text passages could be read with combined use of left and right visual fields in a specific manner; (3) the left visual field was preferred to view stimuli initially presented in left visual space while the right visual field was preferred for words initially presented in right visual space. This effect diminished across sessions. Overall, these findings indicate that (1) a specific viewing strategy can be developed through as little as 5 hours of reading experience without guided training; (2) two distinctly separate retinal areas can be used in an integrated manner during reading; (4) stimulus position in visual space can influence viewing strategy; (5) in general, reading encourages a preference for the inferior over the superior visual field, but not the left over right visual field. Letter/word/text recognition and reading speeds increased progressively across sessions, even after scotoma lateralisation appeared stabilised suggesting that multiple mechanism are involved in adaptive changes.

The reading strategies in individuals with central scotomas and more than one preferred retinal locus (PRL) were investigated using a scanning laser ophthalmoscope in order to understand the visual requirements that lead to the need to use more than one PRL during reading. It was found that: (1) PRL function can be deduced from variation in PRL usage for different size and length of isolated words; (2) each subject used two or more PRL to accomplish the functions of global viewing and discrimination, suggesting that these are two of the minimum requirements for reading; (3) reading strategies can change depending on the position of words in visual space; (4) line-changing strategies can revert to horizontal and vertical component movements. These findings have implications for improving reading performance through training in patients with central scotomas.

A patient with chronic inflammatory demyelinating polyneuropathy (CIDP) presented with an isolated unilateral adduction deficit and ptosis. Investigations were negative until the onset of limb weakness and fatigue 2 years later. At that time, electroneuromyography, cerebrospinal fluid examination, and magnetic resonance imaging confirmed the diagnosis of CIDP. Thus, ophthalmic signs can precede extremity and bulbar signs with a long latency in CIDP.

A 74-year old man presented with horizontal diplopia of sudden onset, worsened by directing gaze to the left. His past medical history included arterial hypertension treated with an angiotensin conversion enzyme inhibitor, a 60pack-per-year smoking history and moderate alcohol consumption. Neurological examination showed moderate left VIth nerve paresis and slight paresis of the right arm and leg. Both spontaneous and voluntary facial movements were normal. Deep tendon reflexes were normal and symmetric. Cutaneous plantar response was flexor on both sides. There was no ataxia or sensory deficit. Gait was unremarkable. Laboratory examinations were normal except for slightly raised liver enzymes. Magnetic resonance imaging, performed 2 days after the onset of symptoms, showed a lesion in the left caudal ventral paramedian pons (Fig. 1a, b). Magnetic resonance angiography as well as extraand intracranial ultrasound with Doppler examination did not reveal any hemodynamically significant arterial stenosis. Heart rhythm remained regular during 24-h monitoring in the stroke unit. The patient was not handicapped by the slight hemiparesis; diplopia resolved partially over several days. Acetylsalicylic acid was introduced.

AIMS To investigate the reading strategy of a patient with central scotoma, using several preferred retinal loci (PRL). METHODS A 47 year old man with Stargardt9s disease was asked to decipher texts projected onto his retina using a scanning laser ophthalmoscope. A recording of the fundus image, on which the projected texts were superimposed, was analysed frame by frame. RESULTS The subject used a combination of three PRL, located above the scotoma and laterally to the left and right of it. He first used his left PRL to search for the beginning of a line, then switched to his right PRL, thus performing an apparent regression which was called “pseudo regression”, to read the line with successive rightward saccades. To decipher a particularly difficult word, he switched to his upper PRL, showing an apparent line loss which was called (“pseudo line loss”), and then used his three PRL in combination. CONCLUSION The patient used a complex, well structured reading strategy. These data showed that backward saccades and unexpected line losses, hitherto thought to be inappropriate and uneconomical, may in fact represent purposeful changes of PRL. It is thought that this is the first structured reading behaviour ever identified in such a condition. Such adaptive oculomotor behaviour should be taken into account when considering rehabilitation procedures.

In 74 normal subjects (62 children aged 5–8 years and 12 adults), we tested the widely-held belief that visual sensitivity improves substantially during childhood. Maturation of the retino-striate pathways is generally invoked to account for age-related changes in visual sensitivity. We evaluated the extent to which attentional factors unduly emphasized the effect of age on the purely physiological mechanisms. After a specially-designed familiarization procedure, sensitivity was fully evaluated at two locations in the superior temporal field using a bracketing technique (Octopus 2000R). False-positive (FP) and false-negative (FN) catch-trials were interspersed with the sequence of stimuli. Analyses demonstrated that: (1) age affected sensitivity; and (2) the general level of attentiveness varied not only with age, but also among subjects in the same age group. We then estimated the extent to which improved visual sensitivity may reflect a concomitant evolution of vigilance. Firstly, controlled variance analyses indicated that factors for evaluating attentiveness (rate of FN responses, slope of the psychometric function at the median, and goodness of fit) were indeed much better predictors than age of the sensitivity measured. Secondly and more significantly, the grouping of subjects into homogeneous subgroups, on the basis of their attentional performance, showed that children as young as 5 years may have a visual sensitivity that is only marginally lower than that of adults.

AIM—To investigate an image distortion, experienced by patients with homonymous paracentral scotomas. METHODS—Two consecutive patients with right inferior homonymous paracentral scotomas resulting from ischaemic brain insults were examined. Neuro-ophthalmological examination included tangent screen and Amsler grid evaluation. In addition, the patients were asked to describe a figure showing two vertical lines, identical in length and symmetrically located on either side of a fixation point. This figure was presented in such a way that when the subject looked at the fixation point the right line crossed the scotoma. Finally, the patients were asked whether, when looking at the face of an interlocutor, both sides of the body looked the same. RESULTS—In both patients field defects were markedly smaller when delineated with Amsler grids than using a tangent screen. With the parallel line test, the right line appeared uninterrupted in patient 1, whereas in patient 2 it looked slightly blurred in a two degree long segment corresponding to the middle of the scotoma. To both subjects the right line appeared shorter than the left line. Finally, both subjects indicated that, after steadily fixating their interlocutor's face or neck for 5-10 seconds, the left shoulder appeared narrower than the right one, which made him look surprisingly thin. This perceptual alteration was called the "thin man" phenomenon. CONCLUSIONS—Paracentral homonymous scotomas can be associated with perceptual completion and shape distortion, owing to apparent displacement of images adjacent to the scotoma towards the field defect. Occurrence of such a perceptual change should alert one to the possibility of paracentral homonymous scotomas, which often go undetected when using routine visual field testing procedures. Keywords: paracentral scotomas; cortical plasticity; "thin man" phenomenon