Radiation-Induced Optic Neuropathy: Clinical and Imaging Profile of Twelve Patients.

BACKGROUND: Radiation-induced optic neuropathy (RON) is a form of delayed radionecrosis of the anterior visual pathways, which develops within months to years after external cranial irradiation and causes severe and irreversible vision loss. Small series reports have adequately documented its clinical features, but imaging characteristics have been less completely described. METHODS: We accrued cases from the University of Michigan Neuro-Ophthalmology Clinic files and from cases coded as "radiation optic neuropathy" at the University of Michigan Medical Center between 1994 and 2017. All patients had undergone 3D-conformal linear accelerator (photon) external beam radiation. We collected clinical details of vision loss, including the temporal relationship to radiation. A single neuroradiologist (E.A.L.) evaluated all available magnetic resonance imaging (MRI) studies, noting the presence of enhancement, expansion, or volume loss of the optic nerves or chiasm, corresponding T2 signal abnormalities, and the absence of demyelination or confounding compressive lesions. RESULTS: Twelve patients (15 eyes) met inclusion criteria. Vision loss was usually monocular at outset, but both optic nerves were eventually involved in 3 (25%) patients. Although usually sudden in onset, vision loss often declined slowly over many months, frequently to finger counting, or worse without recovery. An afferent pupillary defect was always present at the time of presentation. Most affected optic discs were pale at the time of first visual symptoms, indicating that subclinical optic nerve damage had been present for several weeks. The latency from completion of radiation to onset of vision loss ranged from 7 to 48 months (average: 18 months). In 2 patients, radiation was delivered to the whole brain, rather than being limited to the anterior visual pathway. MRI typically displayed a discrete region of enhancement of the affected prechiasmatic optic nerve, often with expansion and high T2 signal in the enhancing segment. In 3 affected eyes, enhancement was apparent on imaging completed 3-6 weeks before the onset of vision loss. In one patient, segmental prechiasmatic enhancement became evident only on repeat MRI completed 7 months after vision loss. The duration of enhancement among 9 eyes with follow-up MRIs was at least 2 months, but in one case, enhancement was still present on a study performed 17 months after treatment. CONCLUSIONS: This study further delineates the profile of RON. Visual loss is often acute, profound, and monocular but may decline slowly after acute onset and later affect both optic nerves. High-resolution MRI of the optic nerves usually will display enhancement of a discrete segment of the intracranial prechiasmatic optic nerve, often with accompanying expansion and T2 hyperintensity. In some cases, these imaging features may precede vision loss. They may be subtle or appear after vision loss. Enhancement lingers for a wide interval, ranging in this study from 2 to at least 17 months. Recognition of these imaging characteristics assists in confirmation of the diagnosis of RON.

Antarctica eye study: a prospective study of the effects of overwintering on ocular parameters and visual function.

BACKGROUND: In 2013 five polar explorers attempted to complete the first Trans-Antarctic Winter Traverse (TAWT). This study presents the ophthalmological findings for this group, who overwintered in Antarctica as part of the White Mars Human Science Protocol. Antarctic crews are exposed to extreme cold, chronic hypoxia and altered day-night cycles. Previous studies of Antarctic explorers have focused on the prolonged effect of ultraviolet radiation including the development of ultraviolet keratitis and accelerated cataract formation. This is the first study of its kind to investigate the effect of overwintering in Antarctica on the human eye. METHODS: Pre and post-expedition clinical observations were made including visual acuity, contrast sensitivity, colour vision, auto-refraction, subjective refraction, retinal examination, retinal autofluoresence and retinal thickness, which were graded for comparison. During the expedition additional observations were made on a monthly basis including LogMAR visual acuity, autorefraction and intraocular pressure. RESULTS: No significant differences between pre and post-expedition observations were found, including visual acuity, contrast sensitivity, colour vision, refraction, visual fields, intraocular pressure and retinal examination. There was a small but statistically significant decrease in retinal thickness across all regions of the retina, except for the macular and fovea, in all explorers. Intra-expedition observations remained within normal limits. CONCLUSION: Reassuringly, the human eye remains largely unchanged by exposure to the extreme conditions encountered during the Antarctic winter, however, further research is needed to investigate changes in retinal thickness. This may have implications for scientists who spend prolonged periods of time in the polar regions, as well as those who have prolonged exposure to the extreme cold or chronic hypoxia in other settings.

Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non-image-forming visual responses, including pupillary constriction, circadian photoentrainment and suppression of pineal melatonin secretion. Five morphological types of ipRGCs, M1-M5, have been identified in mice. In order to understand their functions better, we studied the photoresponses of all five cell types, by whole-cell recording from fluorescently labelled ipRGCs visualized using multiphoton microscopy. All ipRGC types generated melanopsin-based ('intrinsic') as well as synaptically driven ('extrinsic') light responses. The intrinsic photoresponses of M1 cells were lower threshold, higher amplitude and faster than those of M2-M5. The peak amplitudes of extrinsic light responses differed among the ipRGC types; however, the responses of all cell types had comparable thresholds, kinetics and waveforms, and all cells received rod input. While all five types exhibited inhibitory amacrine-cell and excitatory bipolar-cell inputs from the 'on' channel, M1 and M3 received additional 'off'-channel inhibition, possibly through their 'off'-sublamina dendrites. The M2-M5 ipRGCs had centre-surround-organized receptive fields, implicating a capacity to detect spatial contrast. In contrast, the receptive fields of M1 cells lacked surround antagonism, which might be caused by the surround of the inhibitory input nullifying the surround of the excitatory input. All ipRGCs responded robustly to a wide range of motion speeds, and M1-M4 cells appeared tuned to different speeds, suggesting that they might analyse the speed of motion. Retrograde labelling revealed that M1-M4 cells project to the superior colliculus, suggesting that the contrast and motion information signalled by these cells could be used by this sensorimotor area to detect novel objects and motion in the visual field.

New methods devised specify the size and color of the spots monkeys see when striate cortex (area V1) is electrically stimulated.

Creating a prosthetic device for the blind is a central future task. Our research examines the feasibility of producing a prosthetic device based on electrical stimulation of primary visual cortex (area V1), an area that remains intact for many years after loss of vision attributable to damage to the eyes. As an initial step in this effort, we believe that the research should be carried out in animals, as it has been in the creation of the highly successful cochlear implant. We chose the rhesus monkey, whose visual system is similar to that of man. We trained monkeys on two tasks to assess the size, contrast, and color of the percepts created when single sites in area V1 are stimulated through microelectrodes. Here, we report that electrical stimulation within the central 5° of the visual field representation creates a small spot that is between 9 and 26 min of arc in diameter and has a contrast ranging between 2.6% and 10%. The dot generated by the stimulation in the majority of cases was darker than the background viewed by the animal and was composed of a variety of low-contrast colors. These findings can be used as inputs to models of electrical stimulation in area V1. On the basis of these findings, we derive what kinds of images would be expected when implanted arrays of electrodes are stimulated through a camera attached to the head whose images are converted into electrical stimulation using appropriate algorithms.

Radiation optic neuropathy after proton beam therapy for optic nerve sheath meningioma.

A 63-year-old woman with a 1-month history of blurred vision in the right eye was found to have a right optic nerve sheath meningioma. She was treated with fractionated proton beam therapy using a total dose of 50.4 cobalt gray equivalent (CGE) in 1.8 CGE fractions, with subsequent improvement in vision. Twenty-seven months later, the patient reported a 6-week history of progressive blurred vision in her right eye. Magnetic resonance imaging revealed enhancement of the right optic nerve consistent with radiation optic neuropathy (RON). We are unaware of any previous reports of RON when radiotherapy doses fall within the current recommended guidelines of <55 CGE fractionated into daily doses <2 CGE.

Real-world stimuli show perceived hue shifts in the peripheral visual field.

Certain hues undergo shifts in their appearance when they are viewed by the peripheral retina. This has often been shown on a 3-primary color CRT monitor. To investigate the possible role of metamerism, we replicated our peripheral color matching experiments using Munsell paper stimuli viewed under real and simulated daylight (using a 3-primary projection system). Using stimuli of constant value and chroma (7/4), observers adjusted the hue of a 3 deg target presented 18 deg nasally, until it matched a 1 deg target presented 1 deg nasally. The magnitude and pattern of measured hue shifts were similar to those measured using CRT stimuli. We conclude that the perceived hue shifts that have previously been reported in the peripheral retina are independent of the nature of the stimulus and of the illuminant.

The light-induced reduction of horizontal cell receptive field size in the goldfish retina involves nitric oxide.

Horizontal cells of the vertebrate retina have large receptive fields as a result of extensive gap junction coupling. Increased ambient illumination reduces horizontal cell receptive field size. Using the isolated goldfish retina, we have assessed the contribution of nitric oxide to the light-dependent reduction of horizontal cell receptive field size. Horizontal cell receptive field size was assessed by comparing the responses to centered spot and annulus stimuli and from the responses to translated slit stimuli. A period of steady illumination decreased the receptive field size of horizontal cells, as did treatment with the nitric oxide donor (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (100 µM). Blocking the endogenous production of nitric oxide with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (1 mM), decreased the light-induced reduction of horizontal cell receptive field size. These findings suggest that nitric oxide is involved in light-induced reduction of horizontal cell receptive field size.

Spherical arena reveals optokinetic response tuning to stimulus location, size, and frequency across entire visual field of larval zebrafish.

Many animals have large visual fields, and sensory circuits may sample those regions of visual space most relevant to behaviours such as gaze stabilisation and hunting. Despite this, relatively small displays are often used in vision neuroscience. To sample stimulus locations across most of the visual field, we built a spherical stimulus arena with 14,848 independently controllable LEDs. We measured the optokinetic response gain of immobilised zebrafish larvae to stimuli of different steradian size and visual field locations. We find that the two eyes are less yoked than previously thought and that spatial frequency tuning is similar across visual field positions. However, zebrafish react most strongly to lateral, nearly equatorial stimuli, consistent with previously reported spatial densities of red, green, and blue photoreceptors. Upside-down experiments suggest further extra-retinal processing. Our results demonstrate that motion vision circuits in zebrafish are anisotropic, and preferentially monitor areas with putative behavioural relevance.

Temporal Relationship Between Visual Field, Retinal and Microvascular Pathology Following 125I-Plaque Brachytherapy for Uveal Melanoma.

Purpose: To define the temporal relationship of vascular versus neuronal abnormalities in radiation retinopathy. Methods: Twenty-five patients with uveal melanoma treated with brachytherapy and sixteen controls were tested. Functional outcome measures included visual acuity and threshold perimetry (HVF 10-2), while structural outcomes included retinal thickness by OCT and vascular measures by OCT angiography and digital fundus photography. The degree of structural abnormality was determined by intereye asymmetry compared with normal subject asymmetry. Diagnostic sensitivity and specificity of each measure were determined using receiver operating characteristic curves. The relationships between the outcome measures were quantified by Spearman correlation. The effect of time from brachytherapy on visual function, retinal layer thickness, and capillary density was also determined. Results: Within the first 2 years of brachytherapy, outcome measures revealed visual field loss and microvascular abnormalities in 38% and 31% of subjects, respectively. After 2 years, they became more prevalent, increasing to 67% and 67%, respectively, as did retinal thinning (50%). Visual field loss, loss of capillary density, and inner retinal thickness were highly correlated with one another. Diagnostic sensitivity and specificity were highest for abnormalities in digital fundus photography, visual field loss within the central 10°, and decrease in vessel density. Conclusions: Using quantitative approaches, radiation microvasculopathy and visual field defects were detected earlier than loss of inner retinal structure after brachytherapy. Strong correlations eventually developed between vascular pathology, change in retinal thickness, neuronal dysfunction, and radiation dose. Radiation-induced ischemia seems to be a primary early manifestation of radiation retinopathy preceding visual loss.

Single- and Multi-Fraction Stereotactic Radiosurgery Dose Tolerances of the Optic Pathways.

PURPOSE: Dosimetric and clinical predictors of radiation-induced optic nerve/chiasm neuropathy (RION) after single-fraction stereotactic radiosurgery (SRS) or hypofractionated (2-5 fractions) radiosurgery (fSRS) were analyzed from pooled data that were extracted from published reports (PubMed indexed from 1990 to June 2015). This study was undertaken as part of the American Association of Physicists in Medicine Working Group on Stereotactic Body Radiotherapy, investigating normal tissue complication probability (NTCP) after hypofractionated radiation. METHODS AND MATERIALS: Eligible studies described dose delivered to optic nerve/chiasm and provided crude or actuarial toxicity risks, with visual endpoints (ie, loss of visual acuity, alterations in visual fields, and/or blindness/complete vision loss). Studies of patients with optic nerve sheath tumors, optic nerve gliomas, or ocular/uveal melanoma were excluded to obviate direct tumor effects on visual outcomes, as were studies not specifying causes of vision loss (ie, tumor progression vs RION). RESULTS: Thirty-four studies (1578 patients) were analyzed. Histologies included pituitary adenoma, cavernous sinus meningioma, craniopharyngioma, and malignant skull base tumors. Prior resection (76% of patients) did not correlate with RION risk (P = .66). Prior irradiation (6% of patients) was associated with a crude 10-fold increased RION risk versus no prior radiation therapy. In patients with no prior radiation therapy receiving SRS/fSRS in 1-5 fractions, optic apparatus maximum point doses resulting in <1% RION risks include 12 Gy in 1 fraction (which is greater than our recommendation of 10 Gy in 1 fraction), 20 Gy in 3 fractions, and 25 Gy in 5 fractions. Omitting multi-fraction data (and thereby eliminating uncertainties associated with dose conversions), a single-fraction dose of 10 Gy was associated with a 1% RION risk. Insufficient details precluded modeling of NTCP risks after prior radiation therapy. CONCLUSIONS: Optic apparatus NTCP and tolerance doses after single- and multi-fraction stereotactic radiosurgery are presented. Additional standardized dosimetric and toxicity reporting is needed to facilitate future pooled analyses and better define RION NTCP after SRS/fSRS.

Similar effects of repetitive transcranial magnetic stimulation of MT+ and a dorsomedial extrastriate site including V3A on pattern detection and position discrimination of rotating and radial motion patterns.

Our recent psychophysical experiments have identified differences in the spatial summation characteristics of pattern detection and position discrimination tasks performed with rotating, expanding, and contracting stimuli. Areas MT and MST are well established to be involved in processing these stimuli. fMRI results have shown retinotopic activation of area V3A depending on the location of the center of radial motion in vision. This suggests the possibility that V3A may be involved in position discrimination tasks with these motion patterns. Here we use repetitive transcranial magnetic stimulation (rTMS) over MT+ and a dorsomedial extrastriate region including V3A to try to distinguish between TMS effects on pattern detection and position discrimination tasks. If V3A were involved in position discrimination, we would expect to see effects on position discrimination tasks, but not pattern detection tasks, with rTMS over this dorsomedial extrastriate region. In fact, we could not dissociate TMS effects on the two tasks, suggesting that they are performed by the same extrastriate area, in MT+.

Epidemiological study of sun exposure and visual field damage in children in Primorsko-Goranska County--the risk factors of earlier development of macular degeneration.

The aim of this study was to examine the possible harmful effects of solar exposure on visual field damage in children living in Primorsko-Goranska County. Our previous work has shown noxious influence on visual field in children with anamnesis long term exposure to sunlight. This is an extended study, including children in Novi Vinodolski and Gorski kotar. We measured possible defect in isopteric visual field and macular-meridian thresholds. In the area of island of Rab these changes were the biggest, subsequently is Novi Vinodolski and at least Gorski kotar with the smallest range of eye complicates according to exposure to sunlight. These damages correlate with the areas of great solar emission. Damages in periphery isopters of visual field have shown the characteristics of periphery defect invagination, while increased macular thresholds in complete visual field was from 5 to 15Asb. We can conclude that there is direct connection between increased sunlight and long-term exposure to sunlight on one side, and on the other side, damages of retinal perception. Increased sun exposure may represent very important factors in early occurrence and develop of Age-Related Macular Degeneration (AMD). It is recommended the children protection in summer months, as well as taking derivates of vitamin A and antioxidants. Nowadays, AMD is one of the most important causes of damaged visual field, pretend to be national problem if we don't use the adequate prevention. World Health Organization has to begin with prevention of AMD, including these risk factors.

Induced deficits in speed perception by transcranial magnetic stimulation of human cortical areas V5/MT+ and V3A.

In this report, we evaluate the role of visual areas responsive to motion in the human brain in the perception of stimulus speed. We first identified and localized V1, V3A, and V5/MT+ in individual participants on the basis of blood oxygenation level-dependent responses obtained in retinotopic mapping experiments and responses to moving gratings. Repetitive transcranial magnetic stimulation (rTMS) was then used to disrupt the normal functioning of the previously localized visual areas in each participant. During the rTMS application, participants were required to perform delayed discrimination of the speed of drifting or spatial frequency of static gratings. The application of rTMS to areas V5/MT and V3A induced a subjective slowing of visual stimuli and (often) caused increases in speed discrimination thresholds. Deficits in spatial frequency discrimination were not observed for applications of rTMS to V3A or V5/MT+. The induced deficits in speed perception were also specific to the cortical site of TMS delivery. The application of TMS to regions of the cortex adjacent to V5/MT and V3A, as well as to area V1, produced no deficits in speed perception. These results suggest that, in addition to area V5/MT+, V3A plays an important role in a cortical network that underpins the perception of stimulus speed in the human brain.

Visual outcome of a cohort of children with neurofibromatosis type 1 and optic pathway glioma followed by a pediatric neuro-oncology program.

We evaluated the visual outcome of a cohort of children with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) treated according to standardized therapeutic guidelines. The study population consisted of all consecutive patients with NF1 and OPG referred to a specialized pediatric neuro-oncology program between 1994 and 2004. Treatment was instituted only in cases of progressive disease or clinical deterioration. Treatment modalities were chemotherapy (based on vincristine/carboplatin) for children younger than 5 years and radiotherapy for all others. Ten boys and 10 girls (seven with a positive family history) entered the trial (median age at diagnosis of OPG, 29 months). At a median follow-up time of 78 months, seven patients had been treated with chemotherapy only, four with radiotherapy, and four with chemotherapy plus radiotherapy. Five patients were observed only. Currently, 18 are alive and two have died. Eight patients were treated for progressive visual loss in the face of stable disease, five for tumor volume increase without visual deterioration, and two for symptomatic tumor volume increase. At referral, six children had a visual acuity (VA) of < 30% in both eyes; eight children had 100% VA bilaterally. At referral, the visual field (VF) could be assessed in three children: One had VF loss in both eyes, one had VF loss in one eye, and one had normal VF. At last follow-up, eight children had VA < 20% in both eyes; only two children had 100% VA in both eyes. Among 11 children who had some visual function, three had VF loss in one eye and three in both eyes, and five had an intact VF. Contrast and color sensitivity were abnormal in seven and six patients, respectively. Thirteen children fell into the WHO hypovision category. In summary, among the 15 children treated, one had a definitive and two a mild improvement in VA. In conclusion, the visual outcome of this selected cohort of NF1 patients with OPG is unsatisfactory. A critical reappraisal of the therapeutic strategy adopted is needed.

Acidification decouples gap junctions but enlarges the receptive field size of horizontal cells in carp retina.

The receptive field size of retinal horizontal cells is much larger than their dendritic field size due to gap junctional coupling between the same sub-types of cell. Thus, horizontal cells form syncytia by electrical coupling. The basic receptive field profile of horizontal cells can be described by an exponential function based on measurement of responses to a slit of light moved tangentially from a recording electrode. The space constant of this exponential function is proportional to (g(s)/g(m))(1/2), where g(s) and g(m) represent gap junctional conductance and non-gap junctional conductance, respectively. Acidifying the superfusing solution by lowering the pH from 7.60 to 7.30 decreased the dye-coupling, hyperpolarised the resting membrane potential and reduced the photoresponses of H1 type horizontal cells. Surprisingly, however, the receptive field size expanded significantly. Raising the pH from 7.30 to 7.60 or 7.90 produced opposite effects. These results were consistent with alkaline extracellular pH producing a greater increase in g(m) than in g(s) and enhancing release of transmitter from cones acting upon horizontal cells.

Combined proton and photon irradiation for craniopharyngioma: long-term results of the early cohort of patients treated at Harvard Cyclotron Laboratory and Massachusetts General Hospital.

PURPOSE: We report the results of the early cohort of patients treated for craniopharyngioma with combined proton-photon irradiation at the Massachusetts General Hospital and the Harvard Cyclotron Laboratory. METHODS AND MATERIALS: Between 1981 and 1988, 15 patients with craniopharyngioma were treated in part or entirely with fractionated 160 MeV proton beam therapy. The group consisted of 5 children (median age, 15.9 years) and 10 adults (median age, 36.2 years). Median dose prescribed to the tumor was 56.9 cobalt Gray equivalent (CGE; 1 proton Gray = 1.1 CGE). The median proton component was 26.9 CGE. Patients were treated after documented recurrence after initial surgery (n = 6) or after subtotal resection or biopsy (n = 9). None had had prior radiation therapy. RESULTS: Median observation period of surviving patients (n = 11) was 13.1 years from radiotherapy. One patient was lost to follow-up with tumor control after 5.2 years. Actuarial 10-year survival rate was 72%. Four patients have died 5-9.1 years after treatment, two from local failure. Actuarial 5- and 10-year local control rates were 93% and 85%, respectively. The functional status of the living adult patients is unaltered from their preradiotherapy status; all of them continued leading normal or near normal working lives. None of the patients treated as a child had experienced recurrence of tumor. One child shows learning difficulties and slight retardation, comparable to his preradiotherapy status. The others have professional achievements within the normal range. CONCLUSION: Results in terms of survival and local control are comparable with other contemporary series. Although no formal neuropsychological testing was performed, the surrogate measures of lifestyle and professional accomplishments appear to be satisfactory.

Origin of the relative afferent pupillary defect in optic tract lesions.

OBJECTIVE: To determine the percent decussation of pupil input fibers in humans and to explain the size and range of the log unit relative afferent pupillary defect (RAPD) in patients with optic tract lesions. DESIGN: Experimental study. PARTICIPANTS AND CONTROLS: Five patients with a unilateral optic tract lesion. METHODS: The pupil response from light stimulation of the nasal hemifield, temporal hemifield, and full field of each eye of 5 patients with a unilateral optic tract lesion was recorded using computerized binocular infrared pupillography. Six stimulus light intensities, separated by 0.5-log unit steps, were used; 12 stimulus repetitions were given for each stimulus condition. MAIN OUTCOME MEASURES: For each stimulus condition, the pupil response of each eye was characterized by plotting the mean pupil contraction amplitude as a function of stimulus light intensity. The percentage of decussating afferent pupillomotor input fibers was calculated from the ratio of the maximal pupil contractions elicited from each eye. The RAPD was determined pupillographically from full-field stimulation to each eye. RESULTS: In all patients, the pupil response from the functioning temporal hemifield ipsilateral to the tract lesion was greater than that from the functioning contralateral nasal hemifield. This temporal-nasal asymmetry increased with increasing stimulus intensity and was similar in hemifield and full-field stimuli, eventually saturating at maximal light intensity. The log unit RAPD did not correlate with the estimated percentage of decussating pupil fibers, which ranged from 54% to 67%. CONCLUSIONS: In patients with a unilateral optic tract lesion, the pupillary responses from full-field stimulation to each eye are the same as comparing the functioning temporal field with the functioning nasal field. The percentage of decussating fibers is reflected in the ratio of the maximal pupil contraction amplitudes resulting from stimulus input between the two eyes. The RAPD that occurs in this setting reflects the difference in light sensitivity between the intact temporal and nasal hemifields. Its magnitude does not correlate with the difference in the number of crossed and uncrossed axons, but its sidedness contralateral to the side of the optic tract lesion is consistent with the greater percentage of decussating pupillomotor input.

One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering.

The aim of the study was to examine the effect of low-frequency repetitive transcranial magnetic stimulation on saccade triggering. In five participants, a train of 600 pulses with a frequency of 1 Hz was applied over the right frontal eye field and--as control condition--over the vertex. After repetitive transcranial magnetic stimulation application, oculomotor performance was evaluated with an overlap paradigm. The results show that the repetitive transcranial magnetic stimulation effect was specific for frontal eye field stimulation. Saccade latencies were found to be increased bilaterally for several minutes after the stimulation, and the time course of recovery was different for the ipsilateral and contralateral sides. The results are discussed in the light of possible local and remote repetitive transcranial magnetic stimulation effects on the oculomotor network.

Transcranial magnetic stimulation of the left human frontal eye fields eliminates the cost of invalid endogenous cues.

Humans are able to selectively attend to specific regions of space without moving their eyes. However, there is mounting evidence that these covert shifts of attention may employ many of the same brain regions involved when executing the eye movements. For example, functional magnetic resonance imaging (fMRI) studies show that the oculomotor region known as the frontal eye fields (FEF) are activated by the covert shifts of attention. However, it remains possible that the activations seen in these studies result from actively inhibiting eye movements rather than as a direct result of modulating perceptual processing. Here we provide direct evidence for the role of this region in endogenously driven spatial attention. We show that briefly disrupting the left FEFs with transcranial magnetic stimulation (TMS) eliminated the slow response times associated with the invalid strategic cues when the target appeared in the right visual field. At first glance, our findings appear incompatible with the results reported by Grosbras and Paus (Grosbras, M. -H., & Paus, T. (2002). Transcranial magnetic stimulation of the human frontal eye field: effects on visual perception and attention. Journal of Cognitive Neuroscience, 14(7), 1109--1120) and we suggest this is likely due to the design differences. Specifically, we disrupted the FEF at the time of cue onset, rather than target onset. Taken together with the findings of Grosbras and Paus, our findings suggest that the FEF plays an early role in the inhibition of perceptual information. Furthermore, our findings complement work by Ro et al. (Ro, T., Farne, F., & Chang, E. (2003). Inhibition of return and the frontal eye fields. Experimental Brain Research, 150, 290--296) who report that stimulation of the frontal eye fields disrupts the inhibitory consequences of reflexive attention shifts.

Stereotactic radiosurgery for arteriovenous malformations of the postgeniculate visual pathway.

OBJECT: A visual field deficit resulting from the management of an arteriovenous malformation (AVM) significantly impacts a patient's quality of life. The present study was designed to investigate the clinical and radiological outcomes of stereotactic radiosurgery (SRS) performed for AVMs involving the postgeniculate visual pathway. METHODS: In this retrospective single-institution analysis, the authors reviewed their experience with Gamma Knife surgery for postgeniculate visual pathway AVMs performed during the period between 1987 and 2009. RESULTS: During the study interval, 171 patients underwent SRS for AVMs in this region. Forty-one patients (24%) had a visual deficit prior to SRS. The median target volume was 6.0 cm3 (range 0.4-22 cm3), and 19 Gy (range 14-25 Gy) was the median margin dose. Obliteration of the AVM was confirmed in 80 patients after a single SRS procedure at a median follow-up of 74 months (range 5-297 months). The actuarial rate of total obliteration was 67% at 4 years. Arteriovenous malformations with a volume<5 cm3 had obliteration rates of 60% at 3 years and 79% at 4 years. The delivered margin dose proved significant given that 82% of patients receiving ≥22 Gy had complete obliteration. The AVM was completely obliterated in an additional 18 patients after they underwent repeat SRS. At a median of 25 months (range 11-107 months) after SRS, 9 patients developed new or worsened visual field deficits. One patient developed a complete homonymous hemianopia, and 8 patients developed quadrantanopias. The actuarial risk of sustaining a new visual deficit was 3% at 3 years, 5% at 5 years, and 8% at 10 years. Fifteen patients had hemorrhage during the latency period, resulting in death in 9 of the patients. The annual hemorrhage rate during the latency interval was 2%, and no hemorrhages occurred after confirmed obliteration. CONCLUSIONS: Despite an overall treatment mortality of 5%, related to latency interval hemorrhage, SRS was associated with only a 5.6% risk of new visual deficit and a final obliteration rate close to 80% in patients with AVMs of the postgeniculate visual pathway.