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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.

In the highly intricate retinal functional anatomy, connectivity and information processing, the photoreceptor cells play a crucial role. In most simple terms, the photoreceptors rods and cones detect the light and transduce it to the brain as electrical signals through a sophisticated network of neurons. Pathologies that affect the photoreceptor structure and function result in impaired vision. Photoreceptor degeneration due to gene mutations causes a large number of blinding disorders known as inherited retinal dystrophies (IRDs). IRDs affect approximately one in every 3,000 individuals and represent the most frequent inherited forms of human visual handicap [1]. Retinitis pigmentosa (RP), a genetic disease that features degeneration of both rod and cone photoreceptors is the most commonly inherited retinal degeneration, affecting approximately 1.5 million people worldwide [2]. Currently, there is no known effective treatment that can prevent or reverse the vision loss in RP.

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: Use of the antiepileptic drug vigabatrin is associated with an elevated risk of visual field loss. Objective: To determine the frequency of, and risk factors for, vigabatrin-attributed visual field loss (VAVFL) in the setting of a large-scale, multinational, prospective, observational study. Study design: A comparative, open-label, parallel-group, multicentre study. Setting: Hospital outpatient clinics at 46 centres in five countries. Patients: 734 patients with refractory partial epilepsy, divided into three groups and stratified by age (8–12 years; >12 years) and exposure to vigabatrin. Group I comprised patients treated with vigabatrin for ≥6 months. Group II comprised patients previously treated with vigabatrin for ≥6 months who had withdrawn from the drug for ≥6 months. Group III comprised patients never treated with vigabatrin. Patients underwent perimetry at either 4- or 6-month intervals, for up to 36 months. Visual field outcome was evaluated masked to drug exposure. Intervention: Perimetry. Main outcome measure: The visual field outcome at each of four analysis points: (i) at enrolment (i.e. baseline, all patients); (ii) for patients exhibiting a conclusive outcome at the initial visual field examination; (iii) for patients exhibiting at least one conclusive outcome to the visual field examinations; and (iv) at the last conclusive outcome to the visual field examinations. Results: Of the 734 patients, 524 yielded one or more conclusive visual field examinations. For Group I, the frequency of VAVFL at the last conclusive examination was 10/38 (26.3%) for those aged 8–12 years and 65/150 (43.3%) for those aged >12 years. For Group II, the respective frequencies were 7/47 (14.9%) and 37/151 (24.5%). One case resembling VAVFL was present amongst the 186 patients in Group III at the last conclusive examination. The frequency of VAVFL in Groups I and II combined was 20.0% for those aged 8–12 years and 33.9% for those aged >12 years. VAVFL was associated with duration of vigabatrin therapy (odds ratio [OR] up to 15.2; 95% CI 4.4, 51.7), mean daily dose of vigabatrin (OR up to 26.4; 95% CI 2.4, 291.7) and male gender (OR 2.51; 95% CI 1.5, 4.1). VAVFL was more frequently detected with static than with kinetic perimetry (OR up to 0.43; 95% CI 0.24, 0.75). Conclusions: Since the probability of VAVFL is positively associated with treatment duration, careful assessment of the risk-benefit ratio of continuing treatment with vigabatrin is recommended in patients currently receiving this drug. All patients continuing to receive vigabatrin should undergo visual field examination at least every 6 months for the duration of treatment. We recommend two-level (three-zone), gradient-adapted, suprathreshold static perimetry of the peripheral field together with threshold perimetry of the central field out to 30° from fixation. The frequency of ophthalmological and perimetric examinations should be increased in the presence of VAVFL.

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.

Acetylcholine (ACh) has been recognized for a long time as a major neurotransmitter in the retina, however, little is known about the contribution of acetylcholine receptors in synaptic processing. Moreover, even less information is available concerning their role during development. To address this question further, we examined the physiological and pharmacological properties of neuronal nicotinic acetylcholine receptors (nAChRs) in retinal ganglion cells from embryonic (E) 12-18-day-old Leghorn chicks. Patch-clamp recordings in whole-cell configuration revealed that at E12 approximately 21% of the ganglion cells responded to acetylcholine pulses with inward currents. The number of responsive cells progressively increased to 57% at E15 to reach up to 15 positive cells out of 15 cells tested at E18. Acetylcholine-evoked responses could be subdivided, according to their time course, into fast and slowly desensitizing. Taking advantage of the selectivity of the frog toxin epibatidine (Epi), that preferentially activates heteromeric neuronal nicotinic acetylcholine receptors, we compared the currents evoked by this toxin vs. the effects of acetylcholine. A further characterization of the receptor diversity during development was to assess their sensitivity to the alpha-conotoxin MII (alpha-CTX-MII), which has been shown to preferentially block alpha6- and alpha3beta2-containing receptors. These data demonstrate that ganglion cells of the chick retina express multiple receptor subtypes that progressively develop as a function of retina maturation.

Conscious experience is an essential part of normal human life and interaction with the environment. Yet the nature of consciousness and conscious perception remains a mystery. Because of its subjective nature, consciousness has been difficult to investigate scientifically, but clues have been gained through studies involving patients with cortical lesions. During the past decade, the development of event-related fMRI has provided insights into aspects of conscious perception in control subjects and patients with cortical lesions by correlating awareness and performance with neural activity during visual tasks. This article reviews how recent research has advanced understanding of conscious perception, its relationship to neural activity and visual performance, and how this relationship can be altered by visual dysfunction. It also presents recent research about how conscious awareness of vision might be represented at a neural level in the central nervous system.

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.

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.).

In humans, the perception of vertical is provided by input from various sensorineural organs and pathways: vision, eye-movements, and proprioceptive and vestibular cues, particularly from the otolithic organs and graviceptive pathways. Well known in several types of brainstem lesions, subjective visual vertical (SVV) abnormalities may also be observed after peripheral vestibular lesions, such as surgical deafferentation, with a deviation directed toward the operated ear. Subjective visual vertical abnormalities are presumably related to a lesion of the otolithic organs and/or to changes in the afferent graviceptive pathways. The goal of this prospective study was to measure the SVV and to define the influence of the otolithic organs in patients suffering from various types of peripheral vestibular diseases: unilateral sudden cochleo-vestibular loss, so-called "viral labyrinthitis" (VL), sudden idiopathic unilateral peripheral vestibular loss, so-called "vestibular neuritis" (Ne). Data were compared with findings after unilateral surgical deafferentations such as vestibular neurectomy (VN) and labyrinthectomy (Lab). Subjective visual vertical was measured with a binocular test (vertical frame) and a monocular test (Maddox rod). In all patients, after VN and Lab, the SVV showed a 10-30 degrees tilt with the vertical frame (N: 0 +/- 2 degrees), 5-15 degrees with the Maddox rod (N: 0 +/- 4 degrees). With the vertical frame, SVV was tilted > 2 degrees in VL (47%) and in Ne (37%); the Maddox rod showed a > 4 degrees tilt in VL (41%) and in Ne (42%). The tilt was directed toward the affected ear. Our results demonstrate that SVV is frequently tilted in acute peripheral vestibulopathies such as VL and Ne. These findings suggest that otolithic function is implicated in the deficit depending on the extent and/or the localisation of the peripheral vestibular lesion.

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.

In Monet’s painting Impression. Rising Sun, when one steadily fixates the image of a sailor in the center of the picture for several seconds, the solar disk progressively disappears, being replaced in both brightness and color by the surrounding sky. This “filling-in” phenomenon reflects a process of cortical remapping, similar to the one that occurs in the presence of visual field defects. Filling-in is largely ignored by clinicians, despite its major implications in ophthalmologic practice, especially the nonrecognition of visual field deficits. (Surv Ophthalmol 42:449–452, 1998.

Background: We present the description of a successful outcome in a case of varicella-zoster virus (VZV) acute retinal necrosis (ARN). History and signs: A healthy 40-year-old patient was admitted for a VZV retinitis. Therapy and outcome: 10 days after the onset of intravenous (i.v.) acyclovir treatment, new small peripheral retinal necrotic lesions appeared in the right eye. A viral resistance was suspected and the acyclovir therapy was optimised with i.v. foscarnet combined with 2 intravitreal injections of ganciclovir. The outcome was favourable with a final vision of 1.0 after a follow-up of 30 months. No systemic or local complications were observed. Conclusions: VZV ARN is a severe infection with a poor prognosis. This case demonstrates that combination of antiviral therapies given intravenously (acyclovir + foscarnet) and in the vitreous (ganciclovir) may be safe and efficacious in the management of necrotising herpetic retinopathies affecting immunocompetent patients.

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.

We recently observed a female patient who was suffering from acute right peripheral cochleovestibular loss associated with a marked vertical diplopia. Otoneurological examination showed profound deafness, and absence of nystagmic response to caloric and pendular rotatory test in the right ear. Neuroophthalmological examination showed skew deviation with right hypotropia, excyclotorsion, and tilt of the static visual vertical directed to the right side. Immunological and serological examinations were normal. Neurological examination and extensive neuroradiological investigations failed to demonstrate any central nervous system involvement. In this patient, skew deviation and tilt of the static visual vertical were interpreted as signs of an acute unilateral otolithic dysfunction, due to a sudden idiopathic peripheral vestibular loss.

BACKGROUND: Postoperative bacterial endophthalmitis are caused in 80 % of the cases by the patient's own flora. Most of the time, bacterial agents are Gram-positive ((2/3) of cases) and more rarely Gram-negative ((1/3) of cases). Usually, Pseudomonas sp, Proteus sp or Klebsiella sp are isolated, but very rarely Morganella morganii. HISTORY AND SIGNS: We describe a case of a Morganella morganii endophthalmitis which occurred after a vitrectomy. THERAPY AND OUTCOME: Bacterial examinations disclosed the presence of Morganella morganii in the vitreous. An aggressive treatment (intravitreous [ceftazidim, vancomycin], topical [gentamycin, chloramphenicol] and intravenous [imipenem, ofloxacin] antibiotics) was introduced. In spite of this treatment, the outcome was not favorable. CONCLUSIONS: Post-vitrectomy endophthalmitis is very rare and the isolation of a Gram-negative bacteria, in this case Morganella morganii, is infrequent. The outcome of these infections is often poor despite the introduction of a rapid, specific and aggressive treatment.

Background: To describe indocyanine green (ICG) angiography (ICGA) findings and clinical features of endogenous mycotic endophthalmitis. Patients and methods: Two patients (a female 62 years, a male 31 years) were addressed to investigate a progressive unilateral visual loss. Slit-lamp examination disclosed a macular chorioretinitis. A clinical work-up revealed a mycotic infection (Candida albicans). Before treatment an ICGA was performed. Results:ICGA early frames disclosed hypofluorescent lesiohs. Progressively, the lesions were surrounded by a slight hyperfluorescence, although the centre of the lesions was still hypofluorescent. Conclusions: The presence and persistence of a hypofluorescent lesion, after introducing a specific treatment, led us to suspect a necrotic/ischaemic process affecting the choroidal vascular bed. ICGA provided additional information regarding the pathophysiological process and the patient's functional visual recovery.

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.

The authors examined a 45-year-old-woman complaining of a dull pain located in the left retro-orbital area, which had started six months previously. She also reported a progressive blurring of vision in the left eye that had developed over the last two months. She had a history of chronic sinusitis beginning in her twenties. Two years prior to the examinaton she had sustained a minor head injury. Skull X-rays performed at that time showed a mass lesion in the sphenoid sinus, which however was overlooked. The authors found that visual acuity was 20/20 in both eyes and that, with Goldmann kinetic perimetry, the blind spot was enlarged and isopters were moderately constricted in the left eye. CT scan and MRI showed a large homogeneous non-enhancing lesion within the left sphenoid sinus, compressing the left optic nerve. At surgery, an encapsulated cyst was found containing a yellowish material. Histological examination led to a diagnosis of cholesteatoma. To the authors′ knowledge, this is the first descript...

The use of automated perimetry in retinitis pigmentosa (RP) has not become widespread. This is due to what is considered as a relative lack of automated programs designed to evaluate in the entire visual field both discrete abnormalities and pronounced defects, using a reasonably short procedure.Three patients suffering from different forms of retinitis pigmentosa were evaluated by means of the new Octopus program N1. In two patients, visual fields were also evaluated by Goldmann kinetic perimetry. Automated perimetry demonstrated the characteristic pattern of the visual field defects of retinitis pigmentosa as satisfactorily as Goldmann perimetry. Moreover, it provided better analysis of the central visual field, revealing partially preserved areas which were missed by routine kinetic perimetry.Evaluation with the Octopus program N1 required much less time than with regular 4-2-2 programs for automated perimetry, because of a unique combination of screening and quantified strategies. The collected data a...

Radiation-induced optic neuropathy (RION) is a late complication of radiotherapy, resulting in severe visual loss.1 We report a RION case following radiation therapy delivered at a dose widely considered as innocuous, occurring on a background of previous isolated optic neuritis. Increased brain sensitivity to radiation has been observed in patients with multiple sclerosis (MS),2–4 but we are not aware of previously reported cases solely involving the optic nerves (ONs). This aspect deserves consideration when defining therapeutic strategies.

Definition of the problem: Our goal is to determine the minimum of information necessary for elementary reading, using a retinal implant. This concerns particularly the fragmentation (pixellisation) of the presented image and its position in the visual field. Fragmentation corresponds to the number of electrodes available, the position of the image in the visual field is equivalent to the site of the implant on the retina. Material and methods: 10° × 10° windows, containing isolated words or letters, were presented to six healthy subjects on a computer screen. A coupling between the computer and an eye tracker stabilizes these images in an area of the visual field. This coupling constantly corrects the position of the image on the screen according to the direction of gaze. Results: 1) A rapid decrease of the performance is observed at a certain threshold of pixellisation, dependent on the eccentricity of presentation of the images. 2) In central vision, about 400 pixels are sufficient to recognize 80% of the four-letters words. At 10° of eccentricity, about 1225 pixels are needed. 3) An acceptable comprehension of a text (identification of four words out of five), is impossible at eccentricities higher than 10° 4) About 50 pixels are sufficient for a satisfactory recognition of isolated letters, independently of their eccentricity. Conclusion: These data validate the method of investigation and provide valuable indications regarding minimal visual requirements in prosthetic vision.

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.

An increase in short-term fluctuation is a clinically useful clue in the diagnosis of acquired disorders of the visual pathways. However, short-term fluctuation can also be increased in normal subjects by several factors. We found an increase in short-term fluctuation occurred in normal subjects when the visual field was tested using a bright fixation aid. Eight normal subjects underwent automated perimetry with the Octopus 2000R, in which the dimmest (12.5 candelas/m2) and brightest (435 cd/m2) available fixation aids were used. Mean short-term fluctuation values were 1.63 +/- 0.27 dB with the dimmest aid, and were 2.65 +/- 1.26 dB with the brightest aid. The difference was significant using the paired t-test (P = .037). Moreover, mean sensitivity was reduced from 35.67 +/- 2.26 dB to 33.66 +/- 1.71 dB when the brightest fixation aid was used (P = .004). In six of eight subjects, the relative changes in short-term fluctuation after an increase in brightness of the fixation aid were more pronounced than those in mean sensitivity. An increase in intensity of the fixation aid may cause visual changes in normal subjects that resemble those induced by disorders in the visual pathways. Whenever possible, minimal intensity of the fixation aid should be used to allow for an adequate interpretation of short-term fluctuation values.

MEWDS is a benign acquired disorder of the retinal pigment epithelium of unknown etiology which has been first described in 1984. Actually more than 50 cases have been reported worldwide but only 5 cases from Europe. We report 10 other cases of MEWDS, seen in the past 5 years. Their clinical presentation, perimetric and electroretinographic results, as well as their differential diagnosis will be reported.

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.

Although neurologic complications are frequent in the acquired immunodeficiency syndrome, their incidence and progression in early human immunodeficiency virus (HIV) infection remain controversial. The goal of this study was to assess neurologic manifestations in asymptomatic carriers of HIV.We studied 29 HIV-seropositive homosexual men and 33 seronegative homosexual controls by means of neurologic and neuropsychological examinations, magnetic resonance imaging (MRI), and electrophysiologic tests (electroencephalography, multimodal evoked-potential tests, and otoneurologic tests). After six to nine months, the tests were repeated in 27 seropositive men and 30 controls. The investigators were blind to the serologic status of the subjects.The seropositive subjects had a mean CD4+ lymphocyte count of 635 X 10(6) per liter. Neurologic and neuropsychological examination, MRI, and measurements of pattern visual evoked potentials did not show significant differences between the two groups. The latencies of the median-nerve somatosensory evoked potentials were slightly prolonged in the seropositive men. The initial electroencephalogram was judged abnormal in 8 of 27 of the seropositive subjects (30 percent) as compared with none of the controls, with a slowing of fundamental activity, anterior spread [corrected] of alpha rhythm, subnormal reactivity, and unusual anterior theta activities. These findings were confirmed by computerized spectral analysis. The second electroencephalogram was abnormal in 10 of 25 of the seropositive men (40 percent). The otoneurologic evaluation identified abnormalities in the central auditory or vestibulo-ocular pathways in 34 percent of the seropositive men (10 of 29), as compared with 6 percent of the controls (2 of 33), on the first examination and in 44 percent (12 of 27) and 7 percent (2 of 30), respectively, on the second examination. Altogether, electrophysiologic abnormalities were found in 67 percent of the seropositive men (18 of 27) and 10 percent of the controls (3 of 30) (P less than 0.00005).In persons with asymptomatic HIV infection, electrophysiologic tests may be the most sensitive indicators of subclinical neurologic impairment. Electrophysiologic abnormalities are far more common in asymptomatic carriers of HIV than in controls and tend to progress over time.

Study of a father and son who had helicoid peripapillary chorioretinal degeneration suggests that a progressive tearing and retraction of the retinal pigment epithelium or of Bruch's membrane around the optic disk may be involved in the disorder's pathogenesis. We presume that this tearing results primarily from dysplastic abnormalities of the retinal pigment epithelium that surrounds the optic disk. The dystrophic lesions progress slowly and may affect the macula and even the peripheral retina.

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.

The retina contains a mosaic of photoreceptors coupled to a intelligent neural network extracting important information on object edges, movements. This visual information is then transferred to the brain through the optic nerve. In pathologies like age macular degeneration or retinitis pigmentosa, photoreceptor degeneration leaves the retinal neuronal network unstimulated. Retinal prostheses propose to stimulate electrically this neuronal network to restore a useful vision for locomotion and reading. We are testing prototypes of subretinal prostheses on the retina of dystrophic rats with photoreceptor degeneration. Our experiments have enabled us to introduce reproducibly these prototypes into the subretinal space, to observe regularly the implant in vivo and measure longitudinally the electrode impedance. These in vivo measurements can then be correlated with the histological examination of the retinal tissue. In parallel, techniques were implemented to record retinal ganglion cell activity on the isolated retina to test different stimulation protocols. Classic retinal ganglion cell responses can be recorded with these techniques and allow to measure ganglion cell response to electrical stimulation. These studies should therefore contribute to improving the selectivity in the electrode retinal stimulation by retinal prostheses.

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 …